Advertisement

Aging-Related Changes in Cellular and Molecular Mechanisms of Postinfarction Remodeling: Implications for Heart Failure Therapy

  • Henry Han-Jen Shih
  • Andrew J. BoyleEmail author
Chapter

Abstract

The normal course of aging is well known to result in decreased cardiac function; decreased capacity to tolerate insults, such as myocardial infarction (MI); and a higher prevalence of pathological remodeling post-MI. Recent progress in aging biology has allowed investigators to understand the effect of aging from the molecular, organelle, and cellular levels that ultimately result in organ dysfunction. In this chapter, we will review the natural course of cellular and molecular changes in the heart that predispose an aging heart toward adverse remodeling, the age-related differences in the postinfarction remodeling process, the clinical implications of aging and postinfarction remodeling, and future targets for heart failure therapy in the aged population.

Keywords

Stem Cell Stem Cell Therapy Cardiomyocyte Apoptosis Autophagic Cell Death Secretory Leukocyte Protease Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98–102.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Hayakawa K, Takemura G, Koda M, Kawase Y, Maruyama R, Li Y, et al. Sensitivity to apoptosis signal, clearance rate, and ultrastructure of fas ligand-induced apoptosis in in vivo adult cardiac cells. Circulation. 2002;105(25):3039–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Phaneuf S, Leeuwenburgh C. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol. 2002;282(2):R423–30.PubMedGoogle Scholar
  4. 4.
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 2000;403(6765):98–103.PubMedCrossRefGoogle Scholar
  5. 5.
    Ferri KF, Kroemer G. Organelle-specific initiation of cell death pathways. Nat Cell Biol. 2001;3(11):E255–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Centurione L, Antonucci A, Miscia S, Grilli A, Rapino M, Grifone G, et al. Age-related death-survival balance in myocardium: an immunohistochemical and biochemical study. Mech Ageing Dev. 2002;123(4):341–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Shih H, Lee B, Lee RJ, Boyle AJ. The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol. 2011;57(1):9–17.PubMedCrossRefGoogle Scholar
  8. 8.
    Ozawa T. Mitochondrial DNA, mutations and age. Ann N Y Acad Sci. 1998;854:128–54.PubMedCrossRefGoogle Scholar
  9. 9.
    Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;68(6):1560–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 2001;344(23):1750–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Cesselli D, Beltrami AP, D’Aurizio F, Marcon P, Bergamin N, Toffoletto B, et al. Effects of age and heart failure on human cardiac stem cell function. Am J Pathol. 2011;179(1):349–66.PubMedCrossRefGoogle Scholar
  12. 12.
    Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, et al. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res. 2004;94(4):514–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Kajstura J, Gurusamy N, Ogórek B, Goichberg P, Clavo-Rondon C, Hosoda T, et al. Myocyte turnover in the aging human heart. Circ Res. 2010;107(11):1374–86.PubMedCrossRefGoogle Scholar
  14. 14.
    Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Anversa P, Kajstura J, Leri A, Bolli R. Life and death of cardiac stem cells a paradigm shift in cardiac biology. Circulation. 2006;113(11):1451–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Houtgraaf JH, Versmissen J, van der Giessen WJ. A concise review of DNA damage checkpoints and repair in mammalian cells. Cardiovasc Revasc Med. 2006;7(3):165–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Song H, Cha M-J, Song B-W, Kim I-K, Chang W, Lim S, et al. Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. Stem Cells. 2010;28(3):555–63.PubMedGoogle Scholar
  18. 18.
    Dhalla NS, Rangi S, Babick AP, Zieroth S, Elimban V. Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging. Heart Fail Rev. 2012;17(4–5):671–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Janczewski AM, Lakatta EG. Modulation of sarcoplasmic reticulum Ca(2+) cycling in systolic and diastolic heart failure associated with aging. Heart Fail Rev. 2010;15(5):431–45.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, et al. Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol. 2011;46(7):549–59.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Gosse P. Left ventricular hypertrophy as a predictor of cardiovascular risk. J Hypertens Suppl. 2005;23(1):S27–33.PubMedCrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    Hua Y, Zhang Y, Ceylan-Isik AF, Wold LE, Nunn JM, Ren J. Chronic Akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy. Basic Res Cardiol. 2011;106(6):1173–91.PubMedCrossRefGoogle Scholar
  24. 24.
    Latronico MVG, Costinean S, Lavitrano ML, Peschle C, Condorelli G. Regulation of cell size and contractile function by AKT in cardiomyocytes. Ann N Y Acad Sci. 2004;1015:250–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Frangogiannis NG. Matricellular proteins in cardiac adaptation and disease. Physiol Rev. 2012;92(2):635–88.PubMedCrossRefGoogle Scholar
  26. 26.
    Thomas DP, Cotter TA, Li X, McCormick RJ, Gosselin LE. Exercise training attenuates aging-associated increases in collagen and collagen crosslinking of the left but not the right ventricle in the rat. Eur J Appl Physiol. 2001;85(1–2):164–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Jugdutt BI, Jelani A, Palaniyappan A, Idikio H, Uweira RE, Menon V, et al. Aging-related early changes in markers of ventricular and matrix remodeling after reperfused ST-segment elevation myocardial infarction in the canine model: effect of early therapy with an angiotensin II type 1 receptor blocker. Circulation. 2010;122(4):341–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Bujak M, Kweon HJ, Chatila K, Li N, Taffet G, Frangogiannis NG. Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction. J Am Coll Cardiol. 2008;51(14):1384–92.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    de Jong S, van Veen TAB, van Rijen HVM, de Bakker JMT. Fibrosis and cardiac arrhythmias. J Cardiovasc Pharmacol. 2011;57(6):630–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Gould KE, Taffet GE, Michael LH, Christie RM, Konkol DL, Pocius JS, et al. Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure. Am J Physiol Heart Circ Physiol. 2002;282(2):H615–21.PubMedGoogle Scholar
  31. 31.
    Maggioni AP, Maseri A, Fresco C, Franzosi MG, Mauri F, Santoro E, et al. Age-related increase in mortality among patients with first myocardial infarctions treated with thrombolysis. The Investigators of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI-2). N Engl J Med. 1993;329(20):1442–8.PubMedCrossRefGoogle Scholar
  32. 32.
    French JK, Hellkamp AS, Armstrong PW, Cohen E, Kleiman NS, O’Connor CM, et al. Mechanical complications after percutaneous coronary intervention in ST-elevation myocardial infarction (from APEX-AMI). Am J Cardiol. 2010;105(1):59–63.PubMedCrossRefGoogle Scholar
  33. 33.
    Ornato JP, Peberdy MA, Tadler SC, Strobos NC. Factors associated with the occurrence of cardiac arrest during hospitalization for acute myocardial infarction in the second national registry of myocardial infarction in the US. Resuscitation. 2001;48(2):117–23.PubMedCrossRefGoogle Scholar
  34. 34.
    Ezekowitz JA, Kaul P, Bakal JA, Armstrong PW, Welsh RC, McAlister FA. Declining in-hospital mortality and increasing heart failure incidence in elderly patients with first myocardial infarction. J Am Coll Cardiol. 2009;53(1):13–20.PubMedCrossRefGoogle Scholar
  35. 35.
    White HD, Aylward PEG, Huang Z, Dalby AJ, Weaver WD, Barvik S, et al. Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Circulation. 2005;112(22):3391–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Kushner FG, Hand M, Smith Jr SC, King 3rd SB, Anderson JL, Antman EM, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54(23):2205–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Boyle AJ, McNiece IK, Hare JM. Mesenchymal stem cell therapy for cardiac repair. Methods Mol Biol. 2010;660:65–84.PubMedCrossRefGoogle Scholar
  38. 38.
    Ye J, Boyle A, Shih H, Sievers RE, Zhang Y, Prasad M, et al. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury. PLoS ONE. 2012;7(1):e30329.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Maltais S, Tremblay JP, Perrault LP, Ly HQ. The paracrine effect: pivotal mechanism in cell-based cardiac repair. J Cardiovasc Transl Res. 2010;3(6):652–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Zhang S, Sun A, Xu D, Yao K, Huang Z, Jin H, et al. Impact of timing on efficacy and safety of intracoronary autologous bone marrow stem cells transplantation in acute myocardial infarction: a pooled subgroup analysis of randomized controlled trials. Clin Cardiol. 2009;32(8):458–66.PubMedCrossRefGoogle Scholar
  41. 41.
    Doyle B, Sorajja P, Hynes B, Kumar AHS, Araoz PA, Stalboerger PG, et al. Progenitor cell therapy in a porcine acute myocardial infarction model induces cardiac hypertrophy, mediated by paracrine secretion of cardiotrophic factors including TGFbeta1. Stem Cells Dev. 2008;17(5):941–51.PubMedCrossRefGoogle Scholar
  42. 42.
    Moellendorf S, Kessels C, Peiseler L, Raupach A, Jacoby C, Vogt N, et al. IGF-IR signaling attenuates the age-related decline of diastolic cardiac function. Am J Physiol Endocrinol Metab. 2012;303(2):E213–22.PubMedCrossRefGoogle Scholar
  43. 43.
    Cho J, Zhai P, Maejima Y, Sadoshima J. Myocardial injection with GSK-3β-overexpressing bone marrow-derived mesenchymal stem cells attenuates cardiac dysfunction after myocardial infarction. Circ Res. 2011;108(4):478–89.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Schmidt U, del Monte F, Miyamoto MI, Matsui T, Gwathmey JK, Rosenzweig A, et al. Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circulation. 2000;101(7):790–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Narayanan N, Yang C, Xu A. Dexamethasone treatment improves sarcoplasmic reticulum function and contractile performance in aged myocardium. Mol Cell Biochem. 2004;266(1–2):31–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Liu N, Olson EN. MicroRNA regulatory networks in cardiovascular development. Dev Cell. 2010;18(4):510–25.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Zhu H, Fan G-C. Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. Cardiovasc Res. 2012;94(2):284–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.School of Medicine, Tufts UniversityBostonUSA
  2. 2.Department of CardiologyUniversity of Newcastle, John Hunter HospitalNewcastleAustralia

Personalised recommendations