Advertisement

Basic Aspects of Cardiac Remodelling

  • Ecaterina Bontaş
  • Florentina Radu-Ioniţă
  • Alice Munteanu
  • Iancu Mocanu
Chapter

Abstract

It has been defined by Conn and colleagues in 2000 that “Cardiac remodelling may be characterized as genome expression, molecular, cellular and interstitial changes that are manifested clinically as changes in size, shape and function of the heart after cardiac injury”, associated with ventricular dysfunction, malignant arrhythmias and poor prognosis. Conversely, the various definitions of cardiac remodelling stress on common molecular, biochemical, and mechanical pathways. Although the right ventricle and left ventricle show significant distinctions in embryology, form, and function, they have many similar findings when they adjust to damaging loading or when they fail. Having a number of key differentiations in their molecular response to failure this offer a future platform for right ventricle for a particular therapeutic intervention. It has been suggested by Friedberg and Redington in 2014 that “Focus on the molecular pathways specific to the failing right ventricle, and targeting the interactions between both ventricles may guide to successful treatments for the right ventricle and left ventricle failure”. A shortly review is made with updated information for all factors that cause and affect cardiac remodelling process, especially in case of right heart.

Keywords

Right ventricle Cardiac remodeling Heart failure Reverse remodelling Right heart 

References

  1. 1.
    Hochman JS, Bulkley BH. Expansion of acute myocardial infarction: an experimental study. Circulation. 1982;65(7):1446–50.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res. 1985;57(1):84–95.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81(4):1161–72.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999;79(1):215–62.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Roberts CS, Maclean D, Maroko P, Kloner RA. Early and late remodeling of the left ventricle after acute myocardial infarction. Am J Cardiol. 1984;54(3):407–10.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Swynghedauw B. Remodeling of the heart in chronic pressure overload. Basic Res Cardiol. 1991;86(Suppl 1):99–105.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88(2):389–419.  https://doi.org/10.1152/physrev.00017.2007.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7(8):589–600.  https://doi.org/10.1038/nrm1983.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dorn GW, Robbins J, Sugden PH. Phenotyping hypertrophy: eschew obfuscation. Circ Res. 2003;92(11):1171–5.  https://doi.org/10.1161/01.RES.0000077012.11088.BC.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hill JA, Olson EN. Cardiac plasticity. N Engl J Med. 2008;358(13):1370–80.  https://doi.org/10.1056/NEJMra072139.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA. Controversies in ventricular remodelling. Lancet. 2006;367(9507):356–67.  https://doi.org/10.1016/S0140-6736(06)68074-4.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117(13):1717–31.  https://doi.org/10.1161/CIRCULATIONAHA.107.653584.CrossRefGoogle Scholar
  14. 14.
    D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–9.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006;114(13):1417–31.  https://doi.org/10.1161/CIRCULATIONAHA.104.503540.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Machuca TN, de Perrot M. Mechanical support for the failing right ventricle in patients with precapillary pulmonary hypertension. Circulation. 2015;132(6):526–36.  https://doi.org/10.1161/CIRCULATIONAHA.114.012593.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zaffran S, Kelly RG, Meilhac SM, Buckingham ME, Brown NA. Right ventricular myocardium derives from the anterior heart field. Circ Res. 2004;95(3):261–8.  https://doi.org/10.1161/01.RES.0000136815.73623.BE.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Thomas T, Yamagishi H, Overbeek PA, Olson EN, Srivastava D. The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol. 1998;196(2):228–36.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Kondo RP, Dederko DA, Teutsch C, Chrast J, Catalucci D, Chien KR, Giles WR. Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform. J Physiol. 2006;571(Pt 1):131–46.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Friedberg MK, Redington AN. Right versus left ventricular failure: differences, similarities, and interactions. Circulation. 2014;129(9):1033–44.  https://doi.org/10.1161/CIRCULATIONAHA.113.001375.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Iacobazzi D, Suleiman MS, Ghorbel M, George SJ, Caputo M, Tulloh RM. Cellular and molecular basis of RV hypertrophy in congenital heart disease. Heart. 2016;102(1):12–7.  https://doi.org/10.1136/heartjnl-2015-308348.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest. 1997;100(9):2315–24.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Bakerman PR, Stenmark KR, Fisher JH. Alpha-skeletal actin messenger RNA increases in acute right ventricular hypertrophy. Am J Phys. 1990;258(4 Pt 1):L173–8.Google Scholar
  24. 24.
    Bartelds B, Borgdorff MA, Smit-van Oosten A, Takens J, Boersma B, Nederhoff MG, Elzenga NJ, van Gilst WH, De Windt LJ, Berger RM. Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load. Eur J Heart Fail. 2011;13(12):1275–82.  https://doi.org/10.1093/eurjhf/hfr134.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116(3):238–48.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Urashima T, Zhao M, Wagner R, Fajardo G, Farahani S, Quertermous T, Bernstein D. Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis. Am J Physiol Heart Circ Physiol. 2008;295(3):H1351–68.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Ozhan G, Weidinger G. Wnt/β-catenin signaling in heart regeneration. Cell Regen. 2015;4(1):3.CrossRefGoogle Scholar
  28. 28.
    Woodgett JR. Regulation and functions of the glycogen synthase kinase-3 subfamily. Semin Cancer Biol. 1994;5(4):269–75.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 1980;107(2):519–27.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Nagendran J, Gurtu V, Fu DZ, Dyck JR, Haromy A, Ross DB, Rebeyka IM, Michelakis ED. A dynamic and chamber-specific mitochondrial remodeling in right ventricular hypertrophy can be therapeutically targeted. J Thorac Cardiovasc Surg. 2008;136(1):168–78. 178.e1–3CrossRefGoogle Scholar
  31. 31.
    Zornoff LA, Paiva SA, Duarte DR, Spadaro J. Ventricular remodeling after myocardial infarction: concepts and clinical implications. Arq Bras Cardiol. 2009;92(2):150–64.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Mesquita ET, Montera MW, de Souza Neto JD, Bernardez-Pereira S, Freitas AF Jr, Volschan A, Biolo A, Nunes Filho AC, Chagas AC, Jorge AJ, Almeida DR, Arteaga E, dos Santos Junior EG, Fernandes F, Ramires FJ, Bacal F, Tarasoutshi F, Feitosa GS, Villacorta H Jr, Ferreira JF, Vieira JM Jr, Moura LA, Pires LJ, Correia LC, Rohde LE, Rivas M, Moreira Mda C, Kaiser SE, Ferreira SM, Martins SM, Martinez TL. Biomarkers in cardiology--part 1--in heart failure and specific cardiomyopathies. Arq Bras Cardiol. 2014;103(6):451–9.Google Scholar
  33. 33.
    Azevedo PS, Polegato BF, Minicucci MF, Paiva SA, Zornoff LA. Cardiac remodeling: concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arq Bras Cardiol. 2016;106(1):62–9.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Anand IS, Florea VG, Solomon SD, Konstam MA, Udelson JE. Noninvasive assessment of left ventricular remodeling: concepts, techniques, and implications for clinical trials. J Card Fail. 2002;8(6 Suppl):S452–64.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Heusch G, Libby P, Gersh B, Yellon D, Böhm M, Lopaschuk G, Opie L. Cardiovascular remodelling in coronary artery disease and heart failure. Lancet. 2014;383(9932):1933–43.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Sabbah HN, Goldstein S. Ventricular remodelling: consequences and therapy. Eur Heart J. 1993;14(Suppl C):24–9.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Henning RJ. Effects of positive end-expiratory pressure on the right ventricle. J Appl Physiol. 1986;61(3):819–26.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part one. Am J Respir Crit Care Med. 1994;150(3):833–52.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. Circulation. 1993;87(3):755–63.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987;76(1):44–51.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Rumberger JA, Behrenbeck T, Breen JR, Reed JE, Gersh BJ. Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans. J Am Coll Cardiol. 1993;21(3):673–82.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Bussani R, Abbate A, Biondi-Zoccai GG, Dobrina A, Leone AM, Camilot D, Di Marino MP, Baldi F, Silvestri F, Biasucci LM, Baldi A. Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans. J Clin Pathol. 2003;56(9):672–6.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Oakley C. Importance of right ventricular function in congestive heart failure. Am J Cardiol. 1988;62(2):14A–9A.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25(5):1143–53.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Liu L, Eisen HJ. Epidemiology of heart failure and scope of the problem. Cardiol Clin. 2014;32(1):1–8. viiPubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Pimentel M, Zimerman LI, Rohde LE. Stratification of the risk of sudden death in nonischemic heart failure. Arq Bras Cardiol. 2014;103(4):348–57.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Braunwald E. Heart failure. JACC Heart Fail. 2013;1(1):1–20.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    McKay RG, Pfeffer MA, Pasternak RC, Markis JE, Come PC, Nakao S, Alderman JD, Ferguson JJ, Safian RD, Grossman W. Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986;74(4):693–702.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Anversa P, Olivetti G, Capasso JM. Cellular basis of ventricular remodeling after myocardial infarction. Am J Cardiol. 1991;68(14):7D–16D.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56(1):56–64.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Douglas PS, Morrow R, Ioli A, Reichek N. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1989;13(2):311–5.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Mitchell GF, Lamas GA, Vaughan DE, Pfeffer MA. Left ventricular remodeling in the year after first anterior myocardial infarction: a quantitative analysis of contractile segment lengths and ventricular shape. J Am Coll Cardiol. 1992;19(6):1136–44.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Weisman HF, Bush DE, Mannisi JA, Bulkley BH. Global cardiac remodeling after acute myocardial infarction: a study in the rat model. J Am Coll Cardiol. 1985;5(6):1355–62.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Jugdutt BI. Effect of captopril and enalapril on left ventricular geometry, function and collagen during healing after anterior and inferior myocardial infarction in a dog model. J Am Coll Cardiol. 1995;25(7):1718–25.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Sharov VG, Sabbah HN, Shimoyama H, Goussev AV, Lesch M, Goldstein S. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol. 1996;148(1):141–9.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Teiger E, Than VD, Richard L, Wisnewsky C, Tea BS, Gaboury L, Tremblay J, Schwartz K, Hamet P. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest. 1996;97(12):2891–7.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P. Apoptosis in the failing human heart. N Engl J Med. 1997;336(16):1131–41.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT. Cardiac myocyte necrosis induced by angiotensin II. Circ Res. 1991;69(5):1185–95.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Villarreal FJ, Kim NN, Ungab GD, Printz MP, Dillmann WH. Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation. 1993;88(6):2849–61.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Anderson KR, Sutton MG, Lie JT. Histopathological types of cardiac fibrosis in myocardial disease. J Pathol. 1979;128(2):79–85.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Weber KT, Pick R, Silver MA, Moe GW, Janicki JS, Zucker IH, Armstrong PW. Fibrillar collagen and remodeling of dilated canine left ventricle. Circulation. 1990;82(4):1387–401.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest. 2009;135(3):794–804.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Modesti PA, Vanni S, Bertolozzi I, Cecioni I, Lumachi C, Perna AM, Boddi M, Gensini GF. Different growth factor activation in the right and left ventricles in experimental volume overload. Hypertension. 2004;43:101–8.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, Johnson AD, Wagoner LE, Givertz MM, Liang CS, Neibaur M, Haught WH, LeJemtel TH. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. Engl J Med. 2000;343(4):246–53.CrossRefGoogle Scholar
  65. 65.
    Raizada V, Thakore K, Luo W, McGuire PG. Cardiac chamber-specific alterations of ANP and BNP expression with advancing age and with systemic hypertension. Mol Cell Biochem. 2001;216(1-2):137–40.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Reddy S, Zhao M, DQ H, Fajardo G, Hu S, Ghosh Z, Rajagopalan V, JC W, Bernstein D. Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. Physiol Genomics. 2012;44:562–75.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Wang GY, McCloskey DT, Turcato S, Swigart PM, Simpson PC, Baker AJ. Contrasting inotropic responses to alpha1-adrenergic receptor stimulation in left versus right ventricular myocardium. Am J Physiol Heart Circ Physiol. 2006;291:H2013–7.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Irlbeck M, Muhling O, Iwai T, Zimmer HG. Different response of the rat left and right heart to norepinephrine. Cardiovasc Res. 1996;31:157–62.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Michaels AD, Chatterjee K, De Marco T. Effects of intravenous nesiritide on pulmonary vascular hemodynamics in pulmonary hypertension. J Card Fail. 2005;11(6):425–31.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Piao L, Marsboom G, Archer SL. Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure. J Mol Med. 2010;88(10):1011–20.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Drake JI, Bogaard HJ, Mizuno S, Clifton B, Xie B, Gao Y, Dumur CI, Fawcett P, Voelkel NF, Natarajan R. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol. 2011;45(6):1239–47.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Klinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW. Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension. Chest. 2006;129(2):417–25.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Kirk JA, Cingolani OH. Thrombospondins in the transition from myocardial infarction to heart failure. J Mol Cell Cardiol. 2016;90:102–10.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Geva T, Powell AJ, Crawford EC, Chung T, Colan SD. Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging. Circulation. 1998;98(4):339–45.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Rouleau JL, Paradis P, Shenasa H, Juneau C. Faster time to peak tension and velocity of shortening in right versus left ventricular trabeculae and papillary muscles of dogs. Circ Res. 1986;59(5):556–61.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Zak R. Cell proliferation during cardiac growth. Am J Cardiol. 1973;31(2):211–9.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Vanhoutte PM. Endothelium and control of vascular function. State of the art lecture. Hypertension. 1989;13(6 Pt 2):658–67.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991;83(6):1849–65.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Weber KT, Sun Y, Bhattacharya SK, Ahokas RA, Gerling IC. Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat Rev Cardiol. 2013;10(1):15–26.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Owens GK. Growth response of aortic smooth muscle cells in hypertension. In: Lee RMKW, editor. Blood vessel changes in hypertension: structure and function. Boca Raton: CRC Press; 1989. p. 45–63.42.Google Scholar
  81. 81.
    Weber KT, Clark WA, Janicki JS, Shroff SG. Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium. J Cardiovasc Pharmacol. 1987;10(Suppl 6):S37–50.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Olson EN. A decade of discoveries in cardiac biology. Nat Med. 2004;10(5):467–74.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    MacLellan WR, Schneider MD. Genetic dissection of cardiac growth control pathways. Annu Rev Physiol. 2000;62:289–319.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Frey N, Katus HA, Olson EN, Hill JA. Hypertrophy of the heart: a new therapeutic target? Circulation. 2004;109(13):1580–9.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    McMullen JR, Jennings GL. Differences between pathological and physiological cardiac hypertrophy: novel therapeutic strategies to treat heart failure. Clin Exp Pharmacol Physiol. 2007;34(4):255–62.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Li Z, Bing OH, Long X, Robinson KG, Lakatta EG. Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat. Am J Phys. 1997;272(5 Pt 2):H2313–9.Google Scholar
  87. 87.
    MacLellan WR, Schneider MD. Death by design. Programmed cell death in cardiovascular biology and disease. Circ Res. 1997;81(2):137–44.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Frangogiannis NG. Matricellular proteins in cardiac adaptation and disease. Physiol Rev. 2012;92(2):635–88.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Bornstein P. Diversity of function is inherent in matricellular proteins: an appraisal of thrombospondin 1. J Cell Biol. 1995;130(3):503–6.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Bradshaw AD. The role of secreted protein acidic and rich in cysteine (SPARC) in cardiac repair and fibrosis: does expression of SPARC by macrophages influence outcomes? J Mol Cell Cardiol. 2016;93:156–61.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Francis GS, McDonald KM. Left ventricular hypertrophy: an initial response to myocardial injury. Am J Cardiol. 1992;69(18):3G–7G. discussion 7G–9GPubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Sharma K, Kass DA. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circ Res. 2014;115(1):79–96.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Bittel DC, Butler MG, Kibiryeva N, Marshall JA, Chen J, Lofland GK, O’Brien JE Jr. Gene expression in cardiac tissues from infants with idiopathic conotruncal defects. BMC Med Genet. 2011;4(1).  https://doi.org/10.1186/1755-8794-4-1.
  94. 94.
    Kaynak B, von Heydebreck A, Mebus S, Seelow D, Hennig S, Vogel J, Sperling HP, Pregla R, Alexi-Meskishvili V, Hetzer R, Lange PE, Vingron M, Lehrach H, Sperling S. Genome-wide array analysis of normal and malformed human hearts. Circulation. 2003;107(19):2467–74.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Wu Y, Feng W, Zhang H, Li S, Wang D, Pan X, Hu S. Ca2+-regulatory proteins in cardiomyocytes from the right ventricle in children with congenital heart disease. J Transl Med. 2012;10:67.  https://doi.org/10.1186/1479-5876-10-67.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Tekin D, Dursun AD, Xi L. Hypoxia inducible factor 1 (HIF-1) and cardioprotection. Acta Pharmacol Sin. 2010;31(9):1085–94.  https://doi.org/10.1038/aps.2010.132.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Jeewa A, Manickaraj AK, Mertens L, Manlhiot C, Kinnear C, Mondal T, Smythe J, Rosenberg H, Lougheed J, McCrindle BW, van Arsdell G, Redington AN, Mital S. Genetic determinants of right-ventricular remodeling after tetralogy of Fallot repair. Pediatr Res. 2012;72(4):407–13.  https://doi.org/10.1038/pr.2012.95.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Lawler J, Duquette M, Whittaker CA, Adams JC, McHenry K, DeSimone DW. Identification and characterization of thrombospondin-4, a new member of the thrombospondin gene family. J Cell Biol. 1993;120(4):1059–67.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Lawler J, Hynes RO. The structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins. J Cell Biol. 1986;103(5):1635–48.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Adams JC, Lawler J. The thrombospondins. Cold Spring Harb Perspect Biol. 2011;3(10):a009712.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Adams JC. Thrombospondins: multifunctional regulators of cell interactions. Annu Rev Cell Dev Biol. 2001;17:25–51.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Xia Y, Dobaczewski M, Gonzalez-Quesada C, Chen W, Biernacka A, Li N, Lee DW, Frangogiannis NG. Endogenous thrombospondin 1 protects the pressure-overloaded myocardium by modulating fibroblast phenotype and matrix metabolism. Hypertension. 2011;58(5):902–11.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Mustonen E, Aro J, Puhakka J, Ilves M, Soini Y, Leskinen H, Ruskoaho H, Rysä J. Thrombospondin-4 expression is rapidly upregulated by cardiac overload. Biochem Biophys Res Commun. 2008;373(2):186–91.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Melenovsky V, Benes J, Skaroupkova P, Sedmera D, Strnad H, Kolar M, Vlcek C, Petrak J, Benes J Jr, Papousek F, Oliyarnyk O, Kazdova L, Cervenka L. Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats. Mol Cell Biochem. 2011;354(1-2):83–96.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Swinnen M, Vanhoutte D, Van Almen GC, Hamdani N, Schellings MW, D'hooge J, Van der Velden J, Weaver MS, Sage EH, Bornstein P, Verheyen FK, VandenDriessche T, Chuah MK, Westermann D, Paulus WJ, Van de Werf F, Schroen B, Carmeliet P, Pinto YM, Heymans S. Absence of thrombospondin-2 causes age-related dilated cardiomyopathy. Circulation. 2009;120(16):1585–97.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Schroen B, Heymans S, Sharma U, Blankesteijn WM, Pokharel S, Cleutjens JP, Porter JG, Evelo CT, Duisters R, van Leeuwen RE, Janssen BJ, Debets JJ, Smits JF, Daemen MJ, Crijns HJ, Bornstein P, Pinto YM. Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res. 2004;95(5):515–22.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Toth A, Nickson P, Mandl A, Bannister ML, Toth K, Erhardt P. Endoplasmic reticulum stress as a novel therapeutic target in heart diseases. Cardiovasc Hematol Disord Drug Targets. 2007;7:205–18.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Groenendyk J, Sreenivasaiah PK, Kim DH, Agellon LB, Michalak M. Biology of endoplasmic reticulum stress in the heart. Circ Res. 2010;107(10):1185–97.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Frangogiannis NG, Ren G, Dewald O, Zymek P, Haudek S, Koerting A, Winkelmann K, Michael LH, Lawler J, Entman ML. Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation. 2005;111(22):2935–42.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Snider P, Standley KN, Wang J, Azhar M, Doetschman T, Conway SJ. Origin of cardiac fibroblasts and the role of periostin. Circ Res. 2009;105(10):934–47.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol. 2010;225(3):631–7.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Souders CA, Bowers SL, Baudino TA. Cardiac fibroblast: the renaissance cell. Circ Res. 2009;105(12):1164–76.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Chilton L, Giles WR, Smith GL. Evidence of intercellular coupling between co-cultured adult rabbit ventricular myocytes and myofibroblasts. J Physiol. 2007;583(Pt 1):225–36.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Baudino TA, McFadden A, Fix C, Hastings J, Price R, Borg TK. Cell patterning: interaction of cardiac myocytes and fibroblasts in three-dimensional culture. Microsc Microanal. 2008;14(2):117–25.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure. Heart Fail Rev. 2010;15(4):319–29.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Cleutjens JP, Kandala JC, Guarda E, Guntaka RV, Weber KT. Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol. 1995;27(6):1281–92.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Segura AM, Frazier OH, Buja LM. Fibrosis and heart failure. Heart Fail Rev. 2014;19(2):173–85.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Olivetti G, Capasso JM, Sonnenblick EH, Anversa P. Side-to-side slippage of myocytes participates in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res. 1990;67(1):23–34.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Deb A, Ubil E. Cardiac fibroblast in development and wound healing. J Mol Cell Cardiol. 2014;70:47–55.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Spinale FG, Janicki JS, Zile MR. Membrane-associated matrix proteolysis and heart failure. Circ Res. 2013;112(1):195–208.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Tao G, Levay AK, Peacock JD, Huk DJ, Both SN, Purcell NH, Pinto JR, Galantowicz ML, Koch M, Lucchesi PA, Birk DE, Lincoln J. Collagen XIV is important for growth and structural integrity of the myocardium. J Mol Cell Cardiol. 2012;53(5):626–38.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol. 2011;3(1):a004978.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Gil-Cayuela C, Rivera M, Ortega A, Tarazón E, Triviño JC, Lago F, González-Juanatey JR, Almenar L, Martínez-Dolz L, Portolés M. RNA sequencing analysis identifies new human collagen genes involved in cardiac remodeling. Am Coll Cardiol. 2015;65(12):1265–7.CrossRefGoogle Scholar
  124. 124.
    López B, González A, Ravassa S, Beaumont J, Moreno MU, San José G, Querejeta R, Díez J. Circulating biomarkers of myocardial fibrosis: the need for a reappraisal. J Am Coll Cardiol. 2015;65(22):2449–56.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Leask A. Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res. 2015;116(7):1269–76.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Sun Y, Kiani MF, Postlethwaite AE, Weber KT. Infarct scar as living tissue. Basic Res Cardiol. 2002;97(5):343–7.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Zamilpa R, Lindsey ML. Extracellular matrix turnover and signaling during cardiac remodeling following MI: causes and consequences. J Mol Cell Cardiol. 2010;48(3):558–63.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Lindsey ML, Iyer RP, Jung M, DeLeon-Pennell KY, Ma Y. Matrix metalloproteinases as input and output signals for post-myocardial infarction remodeling. J Mol Cell Cardiol. 2016;91:134–40.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Booz GW, Baker KM. Molecular signalling mechanisms controlling growth and function of cardiac fibroblasts. Cardiovasc Res. 1995;30(4):537–43.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Gonzalez-Quesada C, Cavalera M, Biernacka A, Kong P, Lee DW, Saxena A, Frunza O, Dobaczewski M, Shinde A, Frangogiannis NG. Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix in addition to promoting vascular rarefaction through angiopoietin-2 upregulation. Circ Res. 2013;113(12):1331–44.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Ma Y, Yabluchanskiy A, Lindsey ML. Thrombospondin-1: the good, the bad, and the complicated. Circ Res. 2013;113(12):1272–4.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Bein K, Simons M. Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. J Biol Chem. 2000;275(41):32167–73.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Yang Z, Strickland DK, Bornstein P. Extracellular matrix metalloproteinase 2 levels are regulated by the low density lipoprotein-related scavenger receptor and thrombospondin 2. J Biol Chem. 2001;276(11):8403–8.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Hall MC, Young DA, Waters JG, Rowan AD, Chantry A, Edwards DR, Clark IM. The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1. J Biol Chem. 2003;278(12):10304–13.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Leung LL, Nachman RL. Complex formation of platelet thrombospondin with fibrinogen. J Clin Invest. 1982;70(3):542–9.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Mumby SM, Raugi GJ, Bornstein P. Interactions of thrombospondin with extracellular matrix proteins: selective binding to type V collagen. J Cell Biol. 1984;98(2):646–52.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Bale MD, Mosher DF. Effects of thrombospondin on fibrin polymerization and structure. J Biol Chem. 1986;261(2):862–8.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Narouz-Ott L, Maurer P, Nitsche DP, Smyth N, Paulsson M. Thrombospondin-4 binds specifically to both collagenous and non-collagenous extracellular matrix proteins via its C-terminal domains. J Biol Chem. 2000;275(47):37110–7.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Mustonen E, Ruskoaho H, Rysä J. Thrombospondin-4, tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14: novel extracellular matrix modulating factors in cardiac remodelling. Ann Med. 2012;44(8):793–804.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Sawaki D, Hou L, Tomida S, Sun J, Zhan H, Aizawa K, Son BK, Kariya T, Takimoto E, Otsu K, Conway SJ, Manabe I, Komuro I, Friedman SL, Nagai R, Suzuki T. Modulation of cardiac fibrosis by Krüppel-like factor 6 through transcriptional control of thrombospondin 4 in cardiomyocytes. Cardiovasc Res. 2015;107(4):420–30.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122(1):103–11.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Ma Y, de Castro Brás LE, Toba H, Iyer RP, Hall ME, Winniford MD, Lange RA, Tyagi SC, Lindsey ML. Myofibroblasts and the extracellular matrix network in post-myocardial infarction cardiac remodeling. Pflugers Arch. 2014;466(6):1113–27.PubMedPubMedCentralGoogle Scholar
  143. 143.
    Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation. 2013;128(4):388–400.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Wang C, Wang X. The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity. Biochim Biophys Acta. 2015;1852(2):188–94.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Tarone G, Brancaccio M. Keep your heart in shape: molecular chaperone networks for treating heart disease. Cardiovasc Res. 2014;102(3):346–61.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    James TN. Normal and abnormal consequences of apoptosis in the human heart. From postnatal morphogenesis to paroxysmal arrhythmias. Circulation. 1994;90(1):556–73.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996;335(16):1182–9.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Kostin S, Pool L, Elsässer A, Hein S, Drexler HC, Arnon E, Hayakawa Y, Zimmermann R, Bauer E, Klövekorn WP, Schaper J. Myocytes die by multiple mechanisms in failing human hearts. Circ Res. 2003;92(7):715–24.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Frangogiannis NG. Regulation of the inflammatory response in cardiac repair. Circ Res. 2012;110(1):159–73.  https://doi.org/10.1161/CIRCRESAHA.111.243162.CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, Ullmann C, Lorenz-Meyer S, Schaper J. Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol. 2000;32(2):197–208.PubMedCrossRefPubMedCentralGoogle Scholar
  151. 151.
    Black SC, Huang JQ, Rezaiefar P, Radinovic S, Eberhart A, Nicholson DW, Rodger IW. Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after in vivo myocardial ischemia and reperfusion in the rat. J Mol Cell Cardiol. 1998;30(4):733–42.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Dorn GW. Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovasc Res. 2009;81(3):465–73.  https://doi.org/10.1093/cvr/cvn243. CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Maruyama R, Takemura G, Aoyama T, Hayakawa K, Koda M, Kawase Y, Qiu X, Ohno Y, Minatoguchi S, Miyata K, Fujiwara T, Fujiwara H. Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process. Am J Pathol. 2001;159(2):683–91.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, Li H, Kirshenbaum LA, Hahn HS, Robbins J, Jones WK, Dorn GW. Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest. 2007;117(10):2825–33.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Whelan RS, Mani K, Kitsis RN. Nipping at cardiac remodeling. J Clin Invest. 2007;117(10):2751–3.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Dawson DW, Volpert OV, Pearce SF, Schneider AJ, Silverstein RL, Henkin J, Bouck NP. Three distinct D-amino acid substitutions confer potent antiangiogenic activity on an inactive peptide derived from a thrombospondin-1 type 1 repeat. Mol Pharmacol. 1999;55(2):332–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Dawson DW, Pearce SF, Zhong R, Silverstein RL, Frazier WA, Bouck NP. CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol. 1997;138(3):707–17.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Asch AS, Silbiger S, Heimer E, Nachman RL. Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding. Biochem Biophys Res Commun. 1992;182(3):1208–17.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Jiménez B, Volpert OV, Reiher F, Chang L, Muñoz A, Karin M, Bouck N. c-Jun N-terminal kinase activation is required for the inhibition of neovascularization by thrombospondin-1. Oncogene. 2001;20(26):3443–8.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 160.
    Jiménez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med. 2000;6(1):41–8.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Simantov R, Febbraio M, Silverstein RL. The antiangiogenic effect of thrombospondin-2 is mediated by CD36 and modulated by histidine-rich glycoprotein. Matrix Biol. 2005;24(1):27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Yee KO, Connolly CM, Duquette M, Kazerounian S, Washington R, Lawler J. The effect of thrombospondin-1 on breast cancer metastasis. Breast Cancer Res Treat. 2009;114(1):85–96.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 163.
    Primo L, Ferrandi C, Roca C, Marchiò S, di Blasio L, Alessio M, Bussolino F. Identification of CD36 molecular features required for its in vitro angiostatic activity. FASEB J. 2005;19(12):1713–5.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Volpert OV, Zaichuk T, Zhou W, Reiher F, Ferguson TA, Stuart PM, Amin M, Bouck NP. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med. 2002;8(4):349–57.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Zhang P, Shen M, Fernandez-Patron C, Kassiri Z. ADAMs family and relatives in cardiovascular physiology and pathology. J Mol Cell Cardiol. 2016;93:186–99.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011;377(9763):383–92.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Wang L, Zheng J, Bai X, Liu B, Liu CJ, Xu Q, Zhu Y, Wang N, Kong W, Wang X. ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries. Circ Res. 2009;104(5):688–98.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Kessler T, Zhang L, Liu Z, Yin X, Huang Y, Wang Y, Fu Y, Mayr M, Ge Q, Xu Q, Zhu Y, Wang X, Schmidt K, de Wit C, Erdmann J, Schunkert H, Aherrahrou Z, Kong W. ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1. Circulation. 2015;131(13):1191–201.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Iruela-Arispe ML. Regulation of thrombospondin1 by extracellular proteases. Curr Drug Targets. 2008;9(10):863–8.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010;20(2):143–8.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Carra S, Seguin SJ, Landry J. HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy. Autophagy. 2008;4(2):237–9.PubMedCrossRefGoogle Scholar
  172. 172.
    Babu-Narayan SV, Kilner PJ, Li W, Moon JC, Goktekin O, Davlouros PA, Khan M, Ho SY, Pennell DJ, Gatzoulis MA. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome. Circulation. 2006;113(3):405–13.PubMedCrossRefGoogle Scholar
  173. 173.
    Weidemann F, Herrmann S, Störk S, Niemann M, Frantz S, Lange V, Beer M, Gattenlöhner S, Voelker W, Ertl G, Strotmann JM. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation. 2009;120(7):577–84.  https://doi.org/10.1161/CIRCULATIONAHA.108.847772.CrossRefPubMedPubMedCentralGoogle Scholar
  174. 174.
    Hein S, Arnon E, Kostin S, Schönburg M, Elsässer A, Polyakova V, Bauer EP, Klövekorn WP, Schaper J. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003;107(7):984–91.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 175.
    Jellis C, Martin J, Narula J, Marwick TH. Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol. 2010;56(2):89–97.  https://doi.org/10.1016/j.jacc.2010.02.047.CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2014;71(4):549–74.  https://doi.org/10.1007/s00018-013-1349-6.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Li AH, Liu PP, Villarreal FJ, Garcia RA. Dynamic changes in myocardial matrix and relevance to disease: translational perspectives. Circ Res. 2014;114(5):916–27.  https://doi.org/10.1161/CIRCRESAHA.114.302819.CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Weber KT, Pick R, Jalil JE, Janicki JS, Carroll EP. Patterns of myocardial fibrosis. J Mol Cell Cardiol. 1989;21(Suppl 5):121–31.PubMedCrossRefPubMedCentralGoogle Scholar
  179. 179.
    Gyöngyösi M, Winkler J, Ramos I, Do QT, Firat H, McDonald K, González A, Thum T, Díez J, Jaisser F, Pizard A, Zannad F. Myocardial fibrosis: biomedical research from bench to bedside. Eur J Heart Fail. 2017;19(2):177–91.  https://doi.org/10.1002/ejhf.696.CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    Heymans S, González A, Pizard A, Papageorgiou AP, López-Andrés N, Jaisser F, Thum T, Zannad F, Díez J. Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential. Eur J Heart Fail. 2015;17(8):764–71.  https://doi.org/10.1002/ejhf.312.CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Camelliti P, Borg TK, Kohl P. Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res. 2005;65(1):40–51.PubMedCrossRefPubMedCentralGoogle Scholar
  182. 182.
    Lajiness JD, Conway SJ. Origin, development, and differentiation of cardiac fibroblasts. J Mol Cell Cardiol. 2014;70:2–8.  https://doi.org/10.1016/j.yjmcc.2013.11.003.CrossRefPubMedPubMedCentralGoogle Scholar
  183. 183.
    Watson CJ, Phelan D, Collier P, Horgan S, Glezeva N, Cooke G, Xu M, Ledwidge M, McDonald K, Baugh JA. Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta. Connect Tissue Res. 2014;55(3):248–56.  https://doi.org/10.3109/03008207.2014.904856.CrossRefPubMedPubMedCentralGoogle Scholar
  184. 184.
    Brilla CG, Maisch B, Zhou G, Weber KT. Hormonal regulation of cardiac fibroblast function. Eur Heart J. 1995;16(Suppl C):45–50.PubMedCrossRefPubMedCentralGoogle Scholar
  185. 185.
    Schellings MW, Pinto YM, Heymans S. Matricellular proteins in the heart: possible role during stress and remodeling. Cardiovasc Res. 2004;64(1):24–31.PubMedCrossRefPubMedCentralGoogle Scholar
  186. 186.
    Kumarswamy R, Thum T. Non-coding RNAs in cardiac remodeling and heart failure. Circ Res. 2013;113(6):676–89.  https://doi.org/10.1161/CIRCRESAHA.113.300226.CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Robins SP. Biochemistry and functional significance of collagen cross-linking. Biochem Soc Trans. 2007;35(Pt 5):849–52.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Shoulders MD, Raines RT. Collagen structure and stability. Annu Rev Biochem. 2009;78:929–58.  https://doi.org/10.1146/annurev.biochem.77.032207.120833.CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    López B, Querejeta R, González A, Larman M, Díez J. Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage C heart failure: potential role of lysyl oxidase. Hypertension. 2012;60(3):677–83.  https://doi.org/10.1161/HYPERTENSIONAHA.112.196113.CrossRefPubMedPubMedCentralGoogle Scholar
  190. 190.
    Kawara T, Derksen R, de Groot JR, Coronel R, Tasseron S, Linnenbank AC, Hauer RN, Kirkels H, Janse MJ, de Bakker JM. Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation. 2001;104(25):3069–75.PubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Anderson KP, Walker R, Urie P, Ershler PR, Lux RL, Karwandee SV. Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy. J Clin Invest. 1993;92(1):122–40.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE. Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension. 2000;36(2):220–5.PubMedCrossRefPubMedCentralGoogle Scholar
  193. 193.
    Wald RM, Haber I, Wald R, Valente AM, Powell AJ, Geva T. Effects of regional dysfunction and late gadolinium enhancement on global right ventricular function and exercise capacity in patients with repaired tetralogy of Fallot. Circulation. 2009;119(10):1370–7.  https://doi.org/10.1161/CIRCULATIONAHA.108.816546.CrossRefPubMedPubMedCentralGoogle Scholar
  194. 194.
    van Oorschot JW, Gho JM, van Hout GP, Froeling M, Hoefer IE, Doevendans PA, Luijten PR, Chamuleau SA, Zwanenburg JJ, Jansen Of Lorkeers SJ. Endogenous contrast MRI of cardiac fibrosis: beyond late gadolinium enhancement. J Magn Reson Imaging. 2015;41(5):1181–9.  https://doi.org/10.1002/jmri.24715.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Sado DM, Flett AS, Moon JC. Novel imaging techniques for diffuse myocardial fibrosis. Futur Cardiol. 2011;7(5):643–50.  https://doi.org/10.2217/fca.11.45.CrossRefGoogle Scholar
  196. 196.
    Gyöngyösi M, Blanco J, Marian T, Trón L, Petneházy O, Petrasi Z, Hemetsberger R, Rodriguez J, Font G, Pavo IJ, Kertész I, Balkay L, Pavo N, Posa A, Emri M, Galuska L, Kraitchman DL, Wojta J, Huber K, Glogar D. Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging. 2008;1(2):94–103.  https://doi.org/10.1161/CIRCIMAGING.108.797449.CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Rischpler C, Nekolla SG, Dregely I, Schwaiger M. Hybrid PET/MR imaging of the heart: potential, initial experiences, and future prospects. J Nucl Med. 2013;54(3):402–15.  https://doi.org/10.2967/jnumed.112.105353.CrossRefPubMedPubMedCentralGoogle Scholar
  198. 198.
    Li XG, Roivainen A, Bergman J, Heinonen A, Bengel F, Thum T, Knuuti J. Enabling [(18)F]-bicyclo[6.1.0]nonyne for oligonucleotide conjugation for positron emission tomography applications: [(18)F]-anti-microRNA-21 as an example. Chem Commun. 2015;51(48):9821–4.  https://doi.org/10.1039/c5cc02618k.CrossRefGoogle Scholar
  199. 199.
    Fang L, Ellims AH, Moore XL, White DA, Taylor AJ, Chin-Dusting J, Dart AM. Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy. J Transl Med. 2015;13:314.  https://doi.org/10.1186/s12967-015-0672-0.CrossRefPubMedPubMedCentralGoogle Scholar
  200. 200.
    Azevedo CF, Nigri M, Higuchi ML, Pomerantzeff PM, Spina GS, Sampaio RO, Tarasoutchi F, Grinberg M, Rochitte CE. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol. 2010;56(4):278–87.  https://doi.org/10.1016/j.jacc.2009.12.074.CrossRefPubMedPubMedCentralGoogle Scholar
  201. 201.
    Aoki T, Fukumoto Y, Sugimura K, Oikawa M, Satoh K, Nakano M, Nakayama M, Shimokawa H. Prognostic impact of myocardial interstitial fibrosis in non-ischemic heart failure -comparison between preserved and reduced ejection fraction heart failure. Circ J. 2011;75(11):2605–13.PubMedCrossRefPubMedCentralGoogle Scholar
  202. 202.
    van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A. 2006;103(48):18255–60.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD, Golub TR, Pieske B, Pu WT. Altered microRNA expression in human heart disease. Physiol Genomics. 2007;31(3):367–73.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258–67.PubMedCrossRefPubMedCentralGoogle Scholar
  205. 205.
    Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011;469(7330):336–42.  https://doi.org/10.1038/nature09783.CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Li D, Ji L, Liu L, Liu Y, Hou H, Yu K, Sun Q, Zhao Z. Characterization of circulating microRNA expression in patients with a ventricular septal defect. PLoS One. 2014;9(8):e106318.  https://doi.org/10.1371/journal.pone.0106318.CrossRefPubMedPubMedCentralGoogle Scholar
  208. 208.
    Lai CT, Ng EK, Chow PC, Kwong A, Cheung YF. Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries. BMC Cardiovasc Disord. 2013;13:73.  https://doi.org/10.1186/1471-2261-13-73.CrossRefPubMedPubMedCentralGoogle Scholar
  209. 209.
    Tutarel O, Dangwal S, Bretthauer J, Westhoff-Bleck M, Roentgen P, Anker SD, Bauersachs J, Thum T. Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol. 2013;167(1):63–6.  https://doi.org/10.1016/j.ijcard.2011.11.082.CrossRefPubMedPubMedCentralGoogle Scholar
  210. 210.
    Zhang J, Chang JJ, Xu F, Ma XJ, Wu Y, Li WC, Wang HJ, Huang GY, Ma D. MicroRNA deregulation in right ventricular outflow tract myocardium in nonsyndromic tetralogy of fallot. Can J Cardiol. 2013;29(12):1695–703.  https://doi.org/10.1016/j.cjca.2013.07.002.CrossRefPubMedPubMedCentralGoogle Scholar
  211. 211.
    Bittel DC, Kibiryeva N, Marshall JA, O’Brien JE. MicroRNA-421 dysregulation is associated with tetralogy of Fallot. Cells. 2014;3(3):713–23.  https://doi.org/10.3390/cells3030713.CrossRefPubMedPubMedCentralGoogle Scholar
  212. 212.
    Tamura T, Said S, Harris J, Lu W, Gerdes AM. Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system. Circulation. 2000;102(2):253–9.PubMedCrossRefPubMedCentralGoogle Scholar
  213. 213.
    van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007;316(5824):575–9.PubMedCrossRefPubMedCentralGoogle Scholar
  214. 214.
    Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, Olson EN. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 2008;22(23):3242–54.  https://doi.org/10.1101/gad.1738708.CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    Apitz C, Honjo O, Humpl T, Li J, Assad RS, Cho MY, Hong J, Friedberg MK, Redington AN. Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload. J Thorac Cardiovasc Surg. 2012;144(6):1494–501.  https://doi.org/10.1016/j.jtcvs.2012.06.027.CrossRefPubMedPubMedCentralGoogle Scholar
  216. 216.
    Unverferth DV, Fetters JK, Unverferth BJ, Leier CV, Magorien RD, Arn AR, Baker PB. Human myocardial histologic characteristics in congestive heart failure. Circulation. 1983;68(6):1194–200.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM, Stack C, Latimer PA, Olson EN, van Rooij E. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124:1537–47.PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Hwang MW, Matsumori A, Furukawa Y, Ono K, Okada M, Iwasaki A, Hara M, Miyamoto T, Touma M, Sasayama S. Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. J Am Coll Cardiol. 2001;38(5):1546–53.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 219.
    Maekawa Y, Anzai T, Yoshikawa T, Asakura Y, Takahashi T, Ishikawa S, Mitamura H, Ogawa S. Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction:a possible role for left ventricular remodeling. J Am Coll Cardiol. 2002;39(2):241–6.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Hafizi S, Wharton J, Chester AH, Yacoub MH. Profibrotic effects of endothelin-1 via the ETA receptor in cultured human cardiac fibroblasts. Cell Physiol Biochem. 2004;14(4-6):285–92.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Katwa LC. Cardiac myofibroblasts isolated from the site of myocardial infarction express endothelin de novo. Am J Physiol Heart Circ Physiol. 2003;285(3):H1132–9.PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Hsieh PC, Davis ME, Lisowski LK, Lee RT. Endothelial-cardiomyocyte interactions in cardiac development and repair. Annu Rev Physiol. 2006;68:51–66.PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Rich S, McLaughlin VV. Endothelin receptor blockers in cardiovascular disease. Circulation. 2003;108:2184–90.PubMedCrossRefPubMedCentralGoogle Scholar
  224. 224.
    Zolk O, Quattek J, Sitzler G, Schrader T, Nickenig G, et al. Expression of endothelin-1, endothelin-converting enzyme, and endothelin receptors in chronic heart failure. Circulation. 1999;99:2118–23.PubMedCrossRefPubMedCentralGoogle Scholar
  225. 225.
    Leask A. Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res. 2010;106(11):1675–80.  https://doi.org/10.1161/CIRCRESAHA.110.217737. CrossRefPubMedPubMedCentralGoogle Scholar
  226. 226.
    Sütsch G, Kiowski W, Yan XW, Hunziker P, Christen S, Strobel W, Kim JH, Rickenbacher P, Bertel O. Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure. Circulation. 1998;98(21):2262–8.PubMedCrossRefPubMedCentralGoogle Scholar
  227. 227.
    Thomson A. Interleukins. In: Oppenheim JJ, editor. The cytokine handbook. 3rd ed. San Diego: Academic; 1998. p. 146–62.Google Scholar
  228. 228.
    Henry G, Garner WL. Inflammatory mediators in wound healing. Surg Clin North Am. 2003;83(3):483–507.PubMedCrossRefPubMedCentralGoogle Scholar
  229. 229.
    Pietilä K, Hermens WT, Harmoinen A, Baardman T, Pasternack A, Topol EJ, Simoons ML. Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase. Am J Cardiol. 1997;80(8):1075–7.PubMedCrossRefPubMedCentralGoogle Scholar
  230. 230.
    Furman MI, Becker RC, Yarzebski J, Savegeau J, Gore JM, Goldberg RJ. Effect of elevated leukocyte count on in-hospital mortality following acute myocardial infarction. Am J Cardiol. 1996;78(8):945–8.PubMedCrossRefPubMedCentralGoogle Scholar
  231. 231.
    Jordan JE, Zhao ZQ, Vinten-Johansen J. The role of neutrophils in myocardial ischemia-reperfusion injury. Cardiovasc Res. 1999;43(4):860–78.PubMedCrossRefPubMedCentralGoogle Scholar
  232. 232.
    Engler RL. Free radical and granulocyte-mediated injury during myocardial ischemia and reperfusion. Am J Cardiol. 1989;63(10):19E–23E.PubMedCrossRefPubMedCentralGoogle Scholar
  233. 233.
    Lasky LA. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992;258(5084):964–9.PubMedCrossRefPubMedCentralGoogle Scholar
  234. 234.
    Ebnet K, Vestweber D. Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem Cell Biol. 1999;112(1):1–23.PubMedCrossRefPubMedCentralGoogle Scholar
  235. 235.
    Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53(1):31–47.PubMedCrossRefPubMedCentralGoogle Scholar
  236. 236.
    Lefer DJ, Granger DN. Oxidative stress and cardiac disease. Am J Med. 2000;109(4):315–23.PubMedCrossRefPubMedCentralGoogle Scholar
  237. 237.
    Dhalla NS, Elmoselhi AB, Hata T, Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res. 2000;47(3):446–56.PubMedCrossRefPubMedCentralGoogle Scholar
  238. 238.
    Hausenloy DJ, Yellon DM. The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol. 2011;8(11):619–29.PubMedCrossRefPubMedCentralGoogle Scholar
  239. 239.
    Foo RS, Mani K, Kitsis RN. Death begets failure in the heart. J Clin Invest. 2005;115(3):565–71.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Filomeni G, Ciriolo MR. Redox control of apoptosis: an update. Antioxid Redox Signal. 2006;8(11-12):2187–92.PubMedCrossRefPubMedCentralGoogle Scholar
  241. 241.
    Matsuzawa A, Ichijo H. Stress-responsive protein kinases in redox-regulated apoptosis signaling. Antioxid Redox Signal. 2005;7(3-4):472–81.PubMedCrossRefPubMedCentralGoogle Scholar
  242. 242.
    Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005;115(3):500–8.PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, Shah AM. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal. 2006;8(5-6):691–728.PubMedCrossRefPubMedCentralGoogle Scholar
  244. 244.
    Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003;41(12):2164–71.PubMedCrossRefPubMedCentralGoogle Scholar
  245. 245.
    Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol. 2000;20(10):2175–83.PubMedCrossRefPubMedCentralGoogle Scholar
  246. 246.
    Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem. 1996;271(38):23317–21.PubMedCrossRefPubMedCentralGoogle Scholar
  247. 247.
    Görlach A, Brandes RP, Nguyen K, Amidi M, Dehghani F, Busse R. A gp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res. 2000;87(1):26–32.PubMedCrossRefPubMedCentralGoogle Scholar
  248. 248.
    Jones SA, O'Donnell VB, Wood JD, Broughton JP, Hughes EJ, Jones OT. Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Phys. 1996;271(4 Pt 2):H1626–34.Google Scholar
  249. 249.
    Chamseddine AH, Miller FJ Jr. Gp91phox contributes to NADPH oxidase activity in aortic fibroblasts but not smooth muscle cells. Am J Physiol Heart Circ Physiol. 2003;285(6):H2284–9.PubMedCrossRefPubMedCentralGoogle Scholar
  250. 250.
    Wenzel S, Taimor G, Piper HM, Schlüter KD. Redox-sensitive intermediates mediate angiotensin II-induced p38 MAP kinase activation, AP-1 binding activity, and TGF-beta expression in adult ventricular cardiomyocytes. FASEB J. 2001;15(12):2291–3.PubMedCrossRefPubMedCentralGoogle Scholar
  251. 251.
    Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol. 2004;4(3):181–9.PubMedCrossRefPubMedCentralGoogle Scholar
  252. 252.
    Aguirre J, Lambeth JD. Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals. Free Radic Biol Med. 2010;49(9):1342–53.PubMedPubMedCentralCrossRefGoogle Scholar
  253. 253.
    Brandes RP, Weissmann N, Schröder K. NADPH oxidases in cardiovascular disease. Free Radic Biol Med. 2010;49(5):687–706.PubMedCrossRefPubMedCentralGoogle Scholar
  254. 254.
    Geiszt M. NADPH oxidases: new kids on the block. Cardiovasc Res. 2006;71(2):289–99.PubMedCrossRefPubMedCentralGoogle Scholar
  255. 255.
    Kayama Y, Raaz U, Jagger A, Adam M, Schellinger IN, Sakamoto M, Suzuki H, Toyama K, Spin JM, Tsao PS. Diabetic cardiovascular disease induced by oxidative stress. Int J Mol Sci. 2015;16(10):25234–63.  https://doi.org/10.3390/ijms161025234.CrossRefPubMedPubMedCentralGoogle Scholar
  256. 256.
    Lassègue B, San Martín A, Griendling KK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res. 2012;110(10):1364–90.  https://doi.org/10.1161/CIRCRESAHA.111.243972.CrossRefPubMedPubMedCentralGoogle Scholar
  257. 257.
    Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O'Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell. 2008;133(3):462–74.  https://doi.org/10.1016/j.cell.2008.02.048.CrossRefPubMedPubMedCentralGoogle Scholar
  258. 258.
    Gilleron M, Marechal X, Montaigne D, Franczak J, Neviere R, Lancel S. NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis. Biochem Biophys Res Commun. 2009;388(4):727–31.  https://doi.org/10.1016/j.bbrc.2009.08.085.CrossRefPubMedPubMedCentralGoogle Scholar
  259. 259.
    Hayashi H, Kobara M, Abe M, Tanaka N, Gouda E, Toba H, Yamada H, Tatsumi T, Nakata T, Matsubara H. Aldosterone nongenomically produces NADPH oxidase-dependent reactive oxygen species and induces myocyte apoptosis. Hypertens Res. 2008;31(2):363–75.  https://doi.org/10.1291/hypres.31.363.CrossRefPubMedPubMedCentralGoogle Scholar
  260. 260.
    Li Y, Arnold JM, Pampillo M, Babwah AV, Peng T. Taurine prevents cardiomyocyte death by inhibiting NADPH oxidase-mediated calpain activation. Free Radic Biol Med. 2009;46(1):51–61.  https://doi.org/10.1016/j.freeradbiomed.2008.09.025.CrossRefPubMedPubMedCentralGoogle Scholar
  261. 261.
    Murdoch CE, Zhang M, Cave AC, Shah AM. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure. Cardiovasc Res. 2006;71(2):208–15.PubMedCrossRefPubMedCentralGoogle Scholar
  262. 262.
    Akki A, Zhang M, Murdoch C, Brewer A, Shah AM. NADPH oxidase signaling and cardiac myocyte function. J Mol Cell Cardiol. 2009;47(1):15–22.PubMedCrossRefPubMedCentralGoogle Scholar
  263. 263.
    Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL. Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxid Redox Signal. 2011;15(8):2301–33.  https://doi.org/10.1089/ars.2010.3792.CrossRefPubMedPubMedCentralGoogle Scholar
  264. 264.
    Zhang M, Perino A, Ghigo A, Hirsch E, Shah AM. NADPH oxidases in heart failure: poachers or gamekeepers? Antioxid Redox Signal. 2013;18(9):1024–41.  https://doi.org/10.1016/j.yjmcc.2009.04.004. CrossRefPubMedPubMedCentralGoogle Scholar
  265. 265.
    Misra MK, Sarwat M, Bhakuni P, Tuteja R, Tuteja N. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit. 2009;15(10):RA209–19.PubMedPubMedCentralGoogle Scholar
  266. 266.
    Qipshidze N, Tyagi N, Metreveli N, Lominadze D, Tyagi SC. Autophagy mechanism of right ventricular remodeling in murine model of pulmonary artery constriction. Am J Physiol Heart Circ Physiol. 2012;302(3):H688–96.  https://doi.org/10.1152/ajpheart.00777.2011.CrossRefPubMedPubMedCentralGoogle Scholar
  267. 267.
    Borchi E, Bargelli V, Stillitano F, Giordano C, Sebastiani M, Nassi PA, d'Amati G, Cerbai E, Nediani C. Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochim Biophys Acta. 2010;1802(3):331–8.PubMedCrossRefPubMedCentralGoogle Scholar
  268. 268.
    Robbins CS, Swirski FK. The multiple roles of monocyte subsets in steady state and inflammation. Cell Mol Life Sci. 2010;67(16):2685–93.  https://doi.org/10.1007/s00018-010-0375-x.CrossRefPubMedPubMedCentralGoogle Scholar
  269. 269.
    Tsujioka H, Imanishi T, Ikejima H, Kuroi A, Takarada S, Tanimoto T, Kitabata H, Okochi K, Arita Y, Ishibashi K, Komukai K, Kataiwa H, Nakamura N, Hirata K, Tanaka A, Akasaka T. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol. 2009;54(2):130–8.  https://doi.org/10.1016/j.jacc.2009.04.021.CrossRefPubMedPubMedCentralGoogle Scholar
  270. 270.
    Arslan F, Smeets MB, O’Neill LA, Keogh B, McGuirk P, Timmers L, Tersteeg C, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010;121(1):80–90.  https://doi.org/10.1161/CIRCULATIONAHA.109.880187.CrossRefPubMedPubMedCentralGoogle Scholar
  271. 271.
    Mann DL. The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circ Res. 2011;108(9):1133–45.  https://doi.org/10.1161/CIRCRESAHA.110.226936. CrossRefPubMedPubMedCentralGoogle Scholar
  272. 272.
    Andrassy M, Volz HC, Igwe JC, Funke B, Eichberger SN, Kaya Z, Buss S, Autschbach F, Pleger ST, Lukic IK, Bea F, Hardt SE, Humpert PM, Bianchi ME, Mairbäurl H, Nawroth PP, Remppis A, Katus HA, Bierhaus A. High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation. 2008;117(25):3216–26.  https://doi.org/10.1161/CIRCULATIONAHA.108.769331.CrossRefPubMedPubMedCentralGoogle Scholar
  273. 273.
    Gordon JW, Shaw JA, Kirshenbaum LA. Multiple facets of NF-κB in the heart: to be or not to NF-κB. Circ Res. 2011;108(9):1122–32.  https://doi.org/10.1161/CIRCRESAHA.110.226928.CrossRefPubMedPubMedCentralGoogle Scholar
  274. 274.
    Bujak M, Dobaczewski M, Chatila K, Mendoza LH, Li N, Reddy A, Frangogiannis NG. Interleukin-1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol. 2008;173(1):57–67.  https://doi.org/10.2353/ajpath.2008.070974.CrossRefPubMedPubMedCentralGoogle Scholar
  275. 275.
    Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821–32.  https://doi.org/10.1016/j.cell.2010.01.040.CrossRefPubMedGoogle Scholar
  276. 276.
    Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation. 2011;123(6):594–604.  https://doi.org/10.1161/CIRCULATIONAHA.110.982777.CrossRefPubMedGoogle Scholar
  277. 277.
    Frangogiannis NG. Chemokines in ischemia and reperfusion. Thromb Haemost. 2007;97(5):738–47.PubMedCrossRefGoogle Scholar
  278. 278.
    Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood. 1992;80(8):2012–20.PubMedPubMedCentralGoogle Scholar
  279. 279.
    Dewald O, Ren G, Duerr GD, Zoerlein M, Klemm C, Gersch C, Tincey S, Michael LH, Entman ML, Frangogiannis NG. Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol. 2004;164(2):665–77.PubMedPubMedCentralCrossRefGoogle Scholar
  280. 280.
    Rumberger JA. Ventricular dilatation and remodeling after myocardial infarction. Mayo Clin Proc. 1994;69(7):664–74.PubMedCrossRefPubMedCentralGoogle Scholar
  281. 281.
    Aikawa Y, Rohde L, Plehn J, Greaves SC, Menapace F, Arnold MO, Rouleau JL, Pfeffer MA, Lee RT, Solomon SD. Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the Healing and Early Afterload Reducing Trial (HEART): an echocardiography-based structural analysis. Am Heart J. 2001;141(2):234–42.PubMedCrossRefPubMedCentralGoogle Scholar
  282. 282.
    Norton GR, Woodiwiss AJ, Gaasch WH, Mela T, Chung ES, Aurigemma GP, Meyer TE. Heart failure in pressure overload hypertrophy. The relative roles of ventricular remodeling and myocardial dysfunction. J Am Coll Cardiol. 2002;39(4):664–71.PubMedCrossRefPubMedCentralGoogle Scholar
  283. 283.
    Richards AM, Nicholls MG, Troughton RW, Lainchbury JG, Elliott J, Frampton C, Espiner EA, Crozier IG, Yandle TG, Turner J. Antecedent hypertension and heart failure after myocardial infarction. J Am Coll Cardiol. 2002;39(7):1182–8.PubMedCrossRefPubMedCentralGoogle Scholar
  284. 284.
    Cingolani OH, Kirk JA, Seo K, Koitabashi N, Lee DI, Ramirez-Correa G, Bedja D, Barth AS, Moens AL, Kass DA. Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle. Circ Res. 2011;109(12):1410–4.PubMedPubMedCentralCrossRefGoogle Scholar
  285. 285.
    Sayer G, Bhat G. The renin-angiotensin-aldosterone system and heart failure. Cardiol Clin. 2014;32(1):21–32. viiPubMedCrossRefPubMedCentralGoogle Scholar
  286. 286.
    Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AF, Neves LM, Bittencourt MI, Pozzan R, Albuquerque DC. Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. Arq Bras Cardiol. 2014;102(1):70–9.PubMedPubMedCentralGoogle Scholar
  287. 287.
    Florea VG, Cohn JN. The autonomic nervous system and heart failure. Circ Res. 2014;114(11):1815–26.PubMedCrossRefPubMedCentralGoogle Scholar
  288. 288.
    Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311(13):819–23.PubMedCrossRefPubMedCentralGoogle Scholar
  289. 289.
    Vantrimpont P, Rouleau JL, Ciampi A, Harel F, de Champlain J, Bichet D, Moyé LA, Pfeffer M. Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) study. Eur Heart J. 1998;19(10):1552–63.PubMedCrossRefPubMedCentralGoogle Scholar
  290. 290.
    Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986;73(2):257–67.PubMedCrossRefGoogle Scholar
  291. 291.
    Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol. 1992;20(1):248–54.PubMedPubMedCentralCrossRefGoogle Scholar
  292. 292.
    Maeda K, Tsutamoto T, Wada A, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Kinoshita M. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol. 2000;36(5):1587–93.PubMedCrossRefGoogle Scholar
  293. 293.
    Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasahara M, Hashimoto R, Katsuura G, Mukoyama M, Itoh H, Saito Y, Tanaka I, Otani H, Katsuki M. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci U S A. 2000;97(8):4239–44.PubMedPubMedCentralCrossRefGoogle Scholar
  294. 294.
    Yamamoto R, Akazawa H, Fujihara H, Ozasa Y, Yasuda N, Ito K, Kudo Y, Qin Y, Ueta Y, Komuro I. Angiotensin II type 1 receptor signaling regulates feeding behavior through anorexigenic corticotropin-releasing hormone in hypothalamus. J Biol Chem. 2011;286(24):21458–65.PubMedPubMedCentralCrossRefGoogle Scholar
  295. 295.
    Akazawa H, Yasuda N, Komuro I. Mechanisms and functions of agonist-independent activation in the angiotensin II type 1 receptor. Mol Cell Endocrinol. 2009;302(2):140–7.PubMedCrossRefPubMedCentralGoogle Scholar
  296. 296.
    Kamo T, Akazawa H, Komuro I. Pleiotropic effects of angiotensin II receptor signaling in cardiovascular homeostasis and aging. Int Heart J. 2015;56(3):249–54.PubMedCrossRefPubMedCentralGoogle Scholar
  297. 297.
    Ozasa Y, Akazawa H, Qin Y, Tateno K, Ito K, Kudo-Sakamoto Y, Yano M, Yabumoto C, Naito AT, Oka T, Lee JK, Minamino T, Nagai T, Kobayashi Y, Komuro I. Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells. Hypertens Res. 2013;36(10):859–65.PubMedCrossRefPubMedCentralGoogle Scholar
  298. 298.
    Akazawa H, Yano M, Yabumoto C, Kudo-Sakamoto Y, Komuro I. Angiotensin II type 1 and type 2 receptor-induced cell signaling. Curr Pharm Des. 2013;19(17):2988–95.PubMedCrossRefPubMedCentralGoogle Scholar
  299. 299.
    Sato M. Roles of accessory proteins for heterotrimeric G-protein in the development of cardiovascular diseases. Circ J. 2013;77(10):2455–61.PubMedCrossRefPubMedCentralGoogle Scholar
  300. 300.
    Wu J, You J, Wang S, Zhang L, Gong H, Zou Y. Insights into the activation and inhibition of angiotensin II type 1 receptor in the mechanically loaded heart. Circ J. 2014;78(6):1283–9.PubMedCrossRefPubMedCentralGoogle Scholar
  301. 301.
    Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993;75(5):977–84.PubMedCrossRefPubMedCentralGoogle Scholar
  302. 302.
    Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Mizuno T, Takano H, Hiroi Y, Ueki K, Tobe K, et al. Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res. 1995;77(2):258–65.PubMedCrossRefPubMedCentralGoogle Scholar
  303. 303.
    Akazawa H. Mechanisms of cardiovascular homeostasis and pathophysiology--from gene expression, signal transduction to cellular communication. Circ J. 2015;79(12):2529–36.PubMedCrossRefPubMedCentralGoogle Scholar
  304. 304.
    Yasuda N, Miura S, Akazawa H, Tanaka T, Qin Y, Kiya Y, Imaizumi S, Fujino M, Ito K, Zou Y, Fukuhara S, Kunimoto S, Fukuzaki K, Sato T, Ge J, Mochizuki N, Nakaya H, Saku K, Komuro I. Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation. EMBO Rep. 2008;9(2):179–86.PubMedPubMedCentralCrossRefGoogle Scholar
  305. 305.
    Konstam MA, Rousseau MF, Kronenberg MW, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators. Circulation. 1992;86(2):431–8.PubMedCrossRefPubMedCentralGoogle Scholar
  306. 306.
    Greenberg B, Quinones MA, Koilpillai C, Limacher M, Shindler D, Benedict C, Shelton B. Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation. 1995;91(10):2573–81.PubMedCrossRefPubMedCentralGoogle Scholar
  307. 307.
    Hafizi S, Wharton J, Morgan K, Allen SP, Chester AH, Catravas JD, Polak JM, Yacoub MH. Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts. Circulation. 1998;98(23):2553–9.PubMedCrossRefPubMedCentralGoogle Scholar
  308. 308.
    Matsusaka T, Katori H, Inagami T, Fogo A, Ichikawa I. Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice. J Clin Invest. 1999;103(10):1451–8.PubMedPubMedCentralCrossRefGoogle Scholar
  309. 309.
    Sadoshima J, Izumo S. Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res. 1993;73(3):413–23.PubMedCrossRefPubMedCentralGoogle Scholar
  310. 310.
    McEwan PE, Gray GA, Sherry L, Webb DJ, Kenyon CJ. Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo. Circulation. 1998;98(24):2765–73.PubMedCrossRefPubMedCentralGoogle Scholar
  311. 311.
    Kawano H, Do YS, Kawano Y, Starnes V, Barr M, Law RE, Hsueh WA. Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts. Circulation. 2000;101(10):1130–7.PubMedCrossRefPubMedCentralGoogle Scholar
  312. 312.
    Hayashi M, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Tsutsui T, Matsui T, Fujii M, Matsumoto T, Yamamoto T, Horie H, Ohnishi M, Kinoshita M. Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol. 2001;38(5):1375–82.PubMedCrossRefPubMedCentralGoogle Scholar
  313. 313.
    Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol. 2000;32(6):865–79.PubMedCrossRefPubMedCentralGoogle Scholar
  314. 314.
    Fullerton MJ, Funder JW. Aldosterone and cardiac fibrosis: in vitro studies. Cardiovasc Res. 1994;28(12):1863–7.PubMedCrossRefPubMedCentralGoogle Scholar
  315. 315.
    Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000;102(22):2700–6.PubMedCrossRefPubMedCentralGoogle Scholar
  316. 316.
    Altin SE, Schulze PC. Metabolism of the right ventricle and the response to hypertrophy and failure. Prog Cardiovasc Dis. 2012;55(2):229–33.  https://doi.org/10.1016/j.pcad.2012.07.010.CrossRefPubMedPubMedCentralGoogle Scholar
  317. 317.
    Dias CA, Assad RS, Caneo LF, Abduch MC, Aiello VD, Dias AR, Marcial MB, Oliveira SA. Reversible pulmonary trunk banding. II. An experimental model for rapid pulmonary ventricular hypertrophy. J Thorac Cardiovasc Surg. 2002;124(5):999–1006.PubMedCrossRefPubMedCentralGoogle Scholar
  318. 318.
    Taegtmeyer H, Golfman L, Sharma S, Razeghi P, van Arsdall M. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann N Y Acad Sci. 2004;1015:202–13.PubMedCrossRefPubMedCentralGoogle Scholar
  319. 319.
    Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013;113(6):709–24.PubMedPubMedCentralCrossRefGoogle Scholar
  320. 320.
    Barger PM, Kelly DP. PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med. 2000;10(6):238–45.PubMedCrossRefPubMedCentralGoogle Scholar
  321. 321.
    Karbowska J, Kochan Z, Smolenski RT. Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart. Cell Mol Biol Lett. 2003;8(1):49–53.PubMedPubMedCentralGoogle Scholar
  322. 322.
    Campos DH, Leopoldo AS, Lima-Leopoldo AP, Nascimento AF, Oliveira SA Jr, Silva DC, Sugizaki MM, Padovani CR, Cicogna AC. Obesity preserves myocardial function during blockade of the glycolytic pathway. Arq Bras Cardiol. 2014;103(4):330–7.PubMedPubMedCentralGoogle Scholar
  323. 323.
    Azevedo PS, Minicucci MF, Santos PP, Paiva SA, Zornoff LA. Energy metabolism in cardiac remodeling and heart failure. Cardiol Rev. 2013;21(3):135–40.PubMedCrossRefPubMedCentralGoogle Scholar
  324. 324.
    Santos PP, Oliveira F, Ferreira VC, Polegato BF, Roscani MG, Fernandes AA, Modesto P, Rafacho BP, Zanati SG, Di Lorenzo A, Matsubara LS, Paiva SA, Zornoff LA, Minicucci MF, Azevedo PS. The role of lipotoxicity in smoke cardiomyopathy. PLoS One. 2014;9(12):e113739.PubMedPubMedCentralCrossRefGoogle Scholar
  325. 325.
    Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular function and failure: report of a National Heart, Lung and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114(17):1883–91.  https://doi.org/10.1161/CIRCULATIONAHA.106.632208.CrossRefPubMedPubMedCentralGoogle Scholar
  326. 326.
    Nagaya N, Goto Y, Satoh T, et al. Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle. J Nucl Med. 1998;39:1676–80.PubMedPubMedCentralGoogle Scholar
  327. 327.
    Bokhari S, Raina A, Rosenweig EB, et al. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging. 2011;4:641–7.  https://doi.org/10.1161/CIRCIMAGING.110.963207.CrossRefPubMedPubMedCentralGoogle Scholar
  328. 328.
    Can MM, Kaymaz C, Tanboga IH, et al. Increased right ventricular glucose metabolism in patients with pulmonary arterial hypertension. Clin Nucl Med. 2011;36:743–8.  https://doi.org/10.1097/RLU.0b013e3182177389.CrossRefPubMedPubMedCentralGoogle Scholar
  329. 329.
    O’Connor RD, Xu J, Ewald GA, et al. Intramyocardial triglyceride quantification by magnetic resonance spectroscopy: in vivo and ex vivo correlation in human subjects. Magn Reson Med. 2011;65:1234–8.  https://doi.org/10.1002/mrm.22734.CrossRefPubMedPubMedCentralGoogle Scholar
  330. 330.
    Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res. 2014;115:176–88.  https://doi.org/10.1161/CIRCRESAHA.113.301129.CrossRefPubMedPubMedCentralGoogle Scholar
  331. 331.
    Sutendra G, Dromparis P, Paulin R, et al. A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension. J Mol Med. 2013;91(11):1315–27.  https://doi.org/10.1007/s00109-013-1059-4.CrossRefPubMedPubMedCentralGoogle Scholar
  332. 332.
    Wasson S, Reddy HK, Dohrmann ML. Current perspectives of electrical remodeling and its therapeutic implications. J Cardiovasc Pharmacol Ther. 2004;9(2):129–44.PubMedCrossRefPubMedCentralGoogle Scholar
  333. 333.
    Hasenfuss G, Schillinger W, Lehnart SE, et al. Relationship between Na+-Ca2+-exchanger protein levels and diastolic function of failing human myocardium. Circulation. 1999;99(5):641–8.PubMedCrossRefPubMedCentralGoogle Scholar
  334. 334.
    Bers DM, Pogwizd SM, Schlotthauer K. Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure. Basic Res Cardiol. 2002;97(Suppl 1):I36–42.PubMedPubMedCentralGoogle Scholar
  335. 335.
    Wang Z, Nolan B, Kutschke W, Hill JA. Na+-Ca2+ exchanger remodeling in pressure overload cardiac hypertrophy. J Biol Chem. 2001;276(21):17706–11.PubMedCrossRefPubMedCentralGoogle Scholar
  336. 336.
    Houser SR, Freeman AR, Jaegar JM, et al. Resting potential changes associated with Na+-K+ pump in failing heart muscle. Am J Phys. 1981;240(2):H168–76.Google Scholar
  337. 337.
    Matsumoto Y, Aihara H, Yamauchi-Kohno R, et al. Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters. Circulation. 2002;106(5):613–9.PubMedPubMedCentralGoogle Scholar
  338. 338.
    Sipido KR, Volders PG, de Groot SH, et al. Enhanced Ca2+ release and Na+/Ca2+ exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation. 2000;102(17):2137–44.PubMedCrossRefPubMedCentralGoogle Scholar
  339. 339.
    Kalogeropoulos AP, Georgiopoulou VV, Howell S, Pernetz MA, Fisher MR, Lerakis S, Martin RP. Evaluation of right intraventricular dyssynchrony by two-dimensional strain echocardiography in patients with pulmonary arterial hypertension. J Am Soc Echocardiogr. 2008;21(9):1028–34.  https://doi.org/10.1016/j.echo.2008.05.005.CrossRefPubMedPubMedCentralGoogle Scholar
  340. 340.
    López-Candales A, Dohi K, Rajagopalan N, Suffoletto M, Murali S, Gorcsan J, Edelman K. Right ventricular dyssynchrony in patients with pulmonary hypertension is associated with disease severity and functional class. Cardiovasc Ultrasound. 2005;3:23.PubMedPubMedCentralCrossRefGoogle Scholar
  341. 341.
    Vonk-Noordegraaf A, Marcus JT, Gan CT, Boonstra A, Postmus PE. Interventricular mechanical asynchrony due to right ventricular pressure overload in pulmonary hypertension plays an important role in impaired left ventricular filling. Chest. 2005;128(6 Suppl):628S–30S.PubMedCrossRefPubMedCentralGoogle Scholar
  342. 342.
    Feneley MP, Gavaghan TP, Baron DW, Branson JA, Roy PR, Morgan JJ. Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart. Circulation. 1985;71(3):473–80.PubMedCrossRefPubMedCentralGoogle Scholar
  343. 343.
    Marcus JT, Gan CT, Zwanenburg JJ, Boonstra A,Allaart CP, Götte MJ, Vonk-Noordegraaf A.Interventricular mechanical asynchrony in pulmonary arterial hypertension: left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol. 2008;51(7):750–7.  https://doi.org/10.1016/j.jacc.2007.10.041.CrossRefPubMedPubMedCentralGoogle Scholar
  344. 344.
    Peschar M, Vermooy K, Vangat WYR, et al. Absence of reeverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles. Cardiovasc Res. 2003;58(3):510–7.PubMedCrossRefPubMedCentralGoogle Scholar
  345. 345.
    Mayet J, Shahi M, McGrath K, Poulter NR, Sever PS, Foale RA, et al. Left ventricular hypertrophy and QT dispersion in hypertension. Hypertension. 1996;28(5):791–6.PubMedCrossRefPubMedCentralGoogle Scholar
  346. 346.
    Darbar D, Cherry CJ, Kerins DM. QT dispersion is reduced after valve replacement in patients with aortic stenosis. Heart. 1999;82(1):15–8.PubMedPubMedCentralCrossRefGoogle Scholar
  347. 347.
    Reddy HK, Wasson S, Koshy SK, et al. Structural correlates of electrical remodeling in ventricular hypertrophy. Cardiovasc Res. 2003;58(3):495–7.PubMedCrossRefPubMedCentralGoogle Scholar
  348. 348.
    Pries AR, Badimon L, Bugiardini R, Camici PG, Dorobantu M, Duncker DJ, Escaned J, Koller A, Piek JJ, de Wit C. Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur Heart J. 2015;36(45):3134–46.  https://doi.org/10.1093/eurheartj/ehv100.CrossRefPubMedPubMedCentralGoogle Scholar
  349. 349.
    Laughlin MH, Bowles DK, Duncker DJ. The coronary circulation in exercise training. Am J Physiol Heart Circ Physiol. 2012;302(1):H10–23.  https://doi.org/10.1152/ajpheart.00574.2011.CrossRefPubMedPubMedCentralGoogle Scholar
  350. 350.
    Schaper W. Collateral circulation: past and present. Basic Res Cardiol. 2009;104(1):5–21.  https://doi.org/10.1007/s00395-008-0760-x.CrossRefPubMedPubMedCentralGoogle Scholar
  351. 351.
    Pries AR, Reglin B, Secomb TW. Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli. Hypertension. 2005;46(4):725–31.PubMedCrossRefPubMedCentralGoogle Scholar
  352. 352.
    Mulvany MJ. Small artery remodelling in hypertension. Basic Clin Pharmacol Toxicol. 2012;110(1):49–55.  https://doi.org/10.1111/j.1742-7843.2011.00758.x.CrossRefPubMedPubMedCentralGoogle Scholar
  353. 353.
    Zakrzewicz A, Secomb TW, Pries AR. Angioadaptation: keeping the vascular system in shape. News Physiol Sci. 2002;17:197–201.PubMedPubMedCentralGoogle Scholar
  354. 354.
    Koller A. Flow-dependent remodeling of small arteries: the stimuli and the sensors are (still) in question. Circ Res. 2006;99(1):6–9.PubMedCrossRefPubMedCentralGoogle Scholar
  355. 355.
    Pries AR, Reglin B, Secomb TW. Structural adaptation of microvascular networks: functional roles of adaptive responses. Am J Physiol Heart Circ Physiol. 2001;281(3):H1015–25.PubMedCrossRefPubMedCentralGoogle Scholar
  356. 356.
    Hopkins WE, Ochoa LL, Richardson GW, et al. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J Heart Lung Transplant. 1996;15(1 Pt 1):100–5.PubMedPubMedCentralGoogle Scholar
  357. 357.
    Reis Filho JR, Cardoso JN, Cardoso CM, Pereira-Barretto AC. Reverse cardiac remodeling: a marker of better prognosis in heart failure. Arq Bras Cardiol. 2015;104(6):502–6.  https://doi.org/10.5935/abc.20150025. CrossRefPubMedPubMedCentralGoogle Scholar
  358. 358.
    Hellawell JL, Margulies KB. Myocardial reverse remodeling. Cardiovasc Ther. 2012;30(3):172–81.  https://doi.org/10.1111/j.1755-5922.2010.00247.x.CrossRefPubMedPubMedCentralGoogle Scholar
  359. 359.
    Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE. Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol. 2010;56(5):392–406.  https://doi.org/10.1016/j.jacc.2010.05.011.CrossRefPubMedPubMedCentralGoogle Scholar
  360. 360.
    Ruiz-Ortega M, Lorenzo O, Ruperez M, Konig S, Wittig B, Egido J. Angiotensin II activates nuclear transcription factor kappa B through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanisms. Circ Res. 2000;86(12):1266–72.PubMedCrossRefPubMedCentralGoogle Scholar
  361. 361.
    Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, Medford RM. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993;92(4):1866–74.PubMedPubMedCentralCrossRefGoogle Scholar
  362. 362.
    Pi XJ, Chen X. Captopril and ramiprilat protect against free radical injury in isolated working rat hearts. J Mol Cell Cardiol. 1989;21(12):1261–71.PubMedCrossRefPubMedCentralGoogle Scholar
  363. 363.
    Chen F, Castranova V, Shi X, Demers LM. New insights into the role of nuclear factor kappa B, a ubiquitous transcription factor in the initiation of diseases. Clin Chem. 1999;45(1):7–17.PubMedPubMedCentralGoogle Scholar
  364. 364.
    Santi D, Giannetta E, Isidori AM, Vitale C, Aversa A, Simoni M. Therapy of endocrine disease: effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis. Eur J Endocrinol. 2015;172(3):R103–14.  https://doi.org/10.1530/EJE-14-0700.CrossRefPubMedPubMedCentralGoogle Scholar
  365. 365.
    Pofi R, Gianfrilli D, Badagliacca R, Di Dato C, Venneri MA, Giannetta E. Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): how do they work? J Endocrinol Investig. 2016;39(2):131–42.  https://doi.org/10.1007/s40618-015-0339-y.CrossRefGoogle Scholar
  366. 366.
    Nam YJ, Song K, Olson EN. Heart repair by cardiac reprogramming. Nat Med. 2013;19(4):413–5.  https://doi.org/10.1038/nm.3147.CrossRefPubMedPubMedCentralGoogle Scholar
  367. 367.
    Hodgkinson CP, Kang MH, Dal-Pra S, Mirotsou M, Dzau VJ. MicroRNAs and cardiac regeneration. Circ Res. 2015;116(10):1700–11.  https://doi.org/10.1161/CIRCRESAHA.116.304377.CrossRefPubMedPubMedCentralGoogle Scholar
  368. 368.
    Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res. 2012;110(11):1465–73.  https://doi.org/10.1161/CIRCRESAHA.112.269035.CrossRefPubMedPubMedCentralGoogle Scholar
  369. 369.
    Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF. Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci U S A. 2006;103(23):8721–6.PubMedPubMedCentralCrossRefGoogle Scholar
  370. 370.
    Takaya T, Nishi H, Horie T, Ono K, Hasegawa K. Roles of microRNAs and myocardial cell differentiation. Prog Mol Biol Transl Sci. 2012;111:139–52.  https://doi.org/10.1016/B978-0-12-398459-3.00006-X.CrossRefPubMedPubMedCentralGoogle Scholar
  371. 371.
    Joladarashi D, Thandavarayan RA, Babu SS, Krishnamurthy P. Small engine, big power: microRNAs as regulators of cardiac diseases and regeneration. Int J Mol Sci. 2014;15(9):15891–911.  https://doi.org/10.3390/ijms150915891.CrossRefPubMedPubMedCentralGoogle Scholar
  372. 372.
    Katz MG, Fargnoli AS, Pritchette LA, Bridges CR. Gene delivery technologies for cardiac applications. Gene Ther. 2012;19(6):659–69.  https://doi.org/10.1038/gt.2012.11.CrossRefPubMedPubMedCentralGoogle Scholar
  373. 373.
    Küçüker SA, Stetson SJ, Becker KA, Akgül A, Loebe M, Lafuente JA, Noon GP, Koerner MM, Entman ML, Torre-Amione G. Evidence of improved right ventricular structure after LVAD support in patients with end-stage cardiomyopathy. J Heart Lung Transplant. 2004;23(1):28–35.PubMedCrossRefPubMedCentralGoogle Scholar
  374. 374.
    Sachse FB, Torres NS, Savio-Galimberti E, Aiba T, Kass DA, Tomaselli GF, Bridge JH. Subcellular structures and function of myocytes impaired during heart failure are restored by cardiac resynchronization therapy. Circ Res. 2012;110(4):588-97. Circ Res. 2012;110(4):588–97.  https://doi.org/10.1161/CIRCRESAHA.111.257428.CrossRefPubMedPubMedCentralGoogle Scholar
  375. 375.
    Barbone A, Holmes JW, Heerdt PM, et al. Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure: a primary role of mechanical unloading underlying reverse remodeling. Circulation. 2001;104(6):670–5.PubMedCrossRefPubMedCentralGoogle Scholar
  376. 376.
    Klotz S, Naka Y, Oz MC, Burkhoff D. Biventricular assist device-induced right ventricular reverse structural and functional remodeling. J Heart Lung Transplant. 2005;24(9):1195–201.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ecaterina Bontaş
    • 1
  • Florentina Radu-Ioniţă
    • 2
    • 3
  • Alice Munteanu
    • 4
  • Iancu Mocanu
    • 5
  1. 1.“Prof. C.C.Iliescu” Emergency Institute for Cardiovascular Diseases,BucharestRomania
  2. 2.“Titu Maiorescu”, University of MedicineBucharestRomania
  3. 3.“Carol Davila” Central Military Emergency University HospitalBucharestRomania
  4. 4.Department of Interventional Cardiology“Carol Davila” Central Military Emergency University HospitalBucharestRomania
  5. 5.Department of Cardiovascular SurgerySanador HospitalBucharestRomania

Personalised recommendations