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Circulating Exosomes in Cardiovascular Diseases

  • Yihua Bei
  • Ting Chen
  • Daniel Dumitru Banciu
  • Dragos Cretoiu
  • Junjie XiaoEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 998)

Abstract

Circulating exosomes could arrive in distant tissues via blood circulation, thus directly communicating with target cells and rapidly regulating intracellular signalings. Circulating exosomes and exosomal cargos are critically involved in cardiovascular pathophysiology, such as cardiomyocyte hypertrophy, apoptosis, and angiogenesis. Circulating exosomes enriched with various types of biological molecules can be changed not only in the number but also in the composite cargos upon cardiac injury, such as myocardial infarction, myocardial ischemia reperfusion injury, atherosclerosis, hypertension, and sepsis cardiomyopathy, which may further influence cardiomyocyte function and contribute to the pathogenesis of cardiovascular diseases. Thus, exosome-based therapeutic strategy may be used to attenuate myocardial injury and promote cardiac regeneration and repair. Also, more preclinical and clinical studies would be needed to investigate the potential of circulating exosomes as biomarkers for the diagnosis, risk stratification, and prognosis of cardiovascular diseases.

Keywords

Circulating exosomes Myocardial infarction Ischemia reperfusion injury Biomarker 

Notes

Acknowledgements

This work was supported by the grants from National Natural Science Foundation of China (81570362, 91639101 and 81200169 to JJ Xiao and 81400647 to Y Bei), and the development fund for Shanghai talents (to JJ Xiao).

Competing Financial Interests The authors declare no competing financial interests.

References

  1. 1.
    Choi DS, Kim DK, Kim YK, Gho YS (2015) Proteomics of extracellular vesicles: exosomes and ectosomes. Mass Spectrom Rev 34(4):474–490PubMedCrossRefGoogle Scholar
  2. 2.
    Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ventimiglia LN, Alonso MA (2016) Biogenesis and function of T cell-derived exosomes. Front Cell Dev Biol 4:84PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Rayner KJ, Hennessy EJ (2013) Extracellular communication via microRNA: lipid particles have a new message. J Lipid Res 54(5):1174–1181PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Boon RA, Vickers KC (2013) Intercellular transport of microRNAs. Arterioscler Thromb Vasc Biol 33(2):186–192PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Hu G, Drescher KM, Chen XM (2012) Exosomal miRNAs: biological properties and therapeutic potential. Front Genet 3:56PubMedPubMedCentralGoogle Scholar
  7. 7.
    Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M (2013) Analysis of microRNA and protein transfer by exosomes during an immune synapse. Methods Mol Biol 1024:41–51PubMedCrossRefGoogle Scholar
  8. 8.
    Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L (2011) Intracellular and extracellular microRNAs in breast cancer. Clin Chem 57(1):18–32PubMedCrossRefGoogle Scholar
  9. 9.
    Friel AM, Corcoran C, Crown J, O’Driscoll L (2010) Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer. Breast Cancer Res Treat 123(3):613–625PubMedCrossRefGoogle Scholar
  10. 10.
    Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R (2015) Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523(7559):177–182PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Fleury A, Martinez MC, Le Lay S (2014) Extracellular vesicles as therapeutic tools in cardiovascular diseases. Front Immunol 5:370PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659PubMedCrossRefGoogle Scholar
  13. 13.
    Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, Gonzalez MA, Bernad A, Sanchez-Madrid F (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Hessvik NP, Phuyal S, Brech A, Sandvig K, Llorente A (2012) Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta 1819(11–12):1154–1163PubMedCrossRefGoogle Scholar
  15. 15.
    Bellingham SA, Coleman BM, Hill AF (2012) Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res 40(21):10937–10949PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Dong H, Lei J, Ding L, Wen Y, Ju H, Zhang X (2013) MicroRNA: function, detection, and bioanalysis. Chem Rev 113(8):6207–6233PubMedCrossRefGoogle Scholar
  17. 17.
    Ahlin F, Arfvidsson J, Vargas KG, Stojkovic S, Huber K, Wojta J (2016) MicroRNAs as circulating biomarkers in acute coronary syndromes: a review. Vasc Pharmacol 81:15–21CrossRefGoogle Scholar
  18. 18.
    Emanueli C, Shearn AI, Angelini GD, Sahoo S (2015) Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vasc Pharmacol 71:24–30CrossRefGoogle Scholar
  19. 19.
    Zhang H, Xiang M, Meng D, Sun N, Chen S (2016) Inhibition of myocardial ischemia/reperfusion injury by exosomes secreted from mesenchymal stem cells. Stem Cells Int 2016:4328362PubMedPubMedCentralGoogle Scholar
  20. 20.
    Kang K, Ma R, Cai W, Huang W, Paul C, Liang J, Wang Y, Zhao T, Kim HW, Xu M, Millard RW, Wen Z, Wang Y (2015) Exosomes secreted from CXCR4 overexpressing mesenchymal stem cells promote cardioprotection via Akt signaling pathway following myocardial infarction. Stem Cells Int 2015:659890PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Davis ME (2016) Exosomes: what do we love so much about them? Circ Res 119(12):1280–1282PubMedCrossRefGoogle Scholar
  22. 22.
    Emanueli C, Shearn AI, Laftah A, Fiorentino F, Reeves BC, Beltrami C, Mumford A, Clayton A, Gurney M, Shantikumar S, Angelini GD (2016) Coronary artery-bypass-graft surgery increases the plasma concentration of exosomes carrying a cargo of cardiac microRNAs: an example of exosome trafficking out of the human heart with potential for cardiac biomarker discovery. PLoS One 11(4):e0154274PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Lawson C, Vicencio JM, Yellon DM, Davidson SM (2016) Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J Endocrinol 228(2):R57–R71PubMedCrossRefGoogle Scholar
  24. 24.
    Evans S, Mann DL (2013) Circulating p53-responsive microRNAs as predictive biomarkers in heart failure after acute myocardial infarction: the long and arduous road from scientific discovery to clinical utility. Circ Res 113(3):242–244PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Sinning JM, Losch J, Walenta K, Bohm M, Nickenig G, Werner N (2011) Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 32(16):2034–2041Google Scholar
  26. 26.
    Aliotta JM, Pereira M, Wen S, Dooner MS, Del Tatto M, Papa E, Goldberg LR, Baird GL, Ventetuolo CE, Quesenberry PJ, Klinger JR (2016) Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice. Cardiovasc Res 110(3):319–330Google Scholar
  27. 27.
    Abdelwahid E, Kalvelyte A, Stulpinas A, de Carvalho KA, Guarita-Souza LC, Foldes G (2016) Stem cell death and survival in heart regeneration and repair. Apoptosis 21(3):252–268PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, Timmers L, van Rijen HV, Doevendans PA, Pasterkamp G, Lim SK, de Kleijn DP (2013) Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 10(3):301–312PubMedCrossRefGoogle Scholar
  29. 29.
    Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, Torre T, Siclari F, Moccetti T, Vassalli G (2014) Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res 103(4):530–541PubMedCrossRefGoogle Scholar
  30. 30.
    Chen L, Wang Y, Pan Y, Zhang L, Shen C, Qin G, Ashraf M, Weintraub N, Ma G, Tang Y (2013) Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem Biophys Res Commun 431(3):566–571PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Cosme J, Liu PP, Gramolini AO (2013) The cardiovascular exosome: current perspectives and potential. Proteomics 13(10–11):1654–1659PubMedCrossRefGoogle Scholar
  32. 32.
    Ibrahim A, Marban E (2016) Exosomes: fundamental biology and roles in cardiovascular physiology. Annu Rev Physiol 78:67–83PubMedCrossRefGoogle Scholar
  33. 33.
    Zhan R, Leng X, Liu X, Wang X, Gong J, Yan L, Wang L, Wang Y, Wang X, Qian LJ (2009) Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochem Biophys Res Commun 387(2):229–233PubMedCrossRefGoogle Scholar
  34. 34.
    Gupta S, Knowlton AA (2007) HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Phys Heart Circ Phys 292(6):H3052–H3056Google Scholar
  35. 35.
    Waldenstrom A, Genneback N, Hellman U, Ronquist G (2012) Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One 7(4):e34653PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Raimondo F, Morosi L, Chinello C, Magni F, Pitto M (2011) Advances in membranous vesicle and exosome proteomics improving biological understanding and biomarker discovery. Proteomics 11(4):709–720PubMedCrossRefGoogle Scholar
  38. 38.
    Pant S, Hilton H, Burczynski ME (2012) The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol 83(11):1484–1494PubMedCrossRefGoogle Scholar
  39. 39.
    Yamashita T, Kamada H, Kanasaki S, Maeda Y, Nagano K, Abe Y, Inoue M, Yoshioka Y, Tsutsumi Y, Katayama S, Inoue M, Tsunoda S (2013) Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Pharmazie 68(12):969–973PubMedGoogle Scholar
  40. 40.
    Molkentin JD, Dorn GW 2nd (2001) Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 63:391–426PubMedCrossRefGoogle Scholar
  41. 41.
    Sahoo S, Losordo DW (2014) Exosomes and cardiac repair after myocardial infarction. Circ Res 114(2):333–344PubMedCrossRefGoogle Scholar
  42. 42.
    Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T (2011) Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 4(4):446–454PubMedCrossRefGoogle Scholar
  43. 43.
    Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048):214–220PubMedCrossRefGoogle Scholar
  44. 44.
    Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Hoydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13(5):613–618PubMedCrossRefGoogle Scholar
  45. 45.
    Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100(3):416–424PubMedCrossRefGoogle Scholar
  46. 46.
    Bagnall RD, Tsoutsman T, Shephard RE, Ritchie W, Semsarian C (2012) Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure. PLoS One 7(9):e44744PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, Holzmann A, Just A, Remke J, Zimmer K, Zeug A, Ponimaskin E, Schmiedl A, Yin X, Mayr M, Halder R, Fischer A, Engelhardt S, Wei Y, Schober A, Fiedler J, Thum T (2014) Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Investig 124(5):2136–2146PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Pan W, Zhong Y, Cheng C, Liu B, Wang L, Li A, Xiong L, Liu S (2013) MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy. PLoS One 8(1):e53950PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Buja LM (2005) Myocardial ischemia and reperfusion injury. Cardiovasc Pathol 14(4):170–175PubMedCrossRefGoogle Scholar
  50. 50.
    Arumugam S, Mito S, Thandavarayan RA, Giridharan VV, Pitchaimani V, Karuppagounder V, Harima M, Nomoto M, Suzuki K, Watanabe K (2013) Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK-mediated apoptosis. Cardiovasc Ther 31(6):352–362PubMedCrossRefGoogle Scholar
  51. 51.
    Kwak HB (2013) Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil 9(2):212–219PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Buja LM (1998) Modulation of the myocardial response to ischemia. Lab Investig 78(11):1345–1373PubMedGoogle Scholar
  53. 53.
    Reimer KA, Ideker RE (1987) Myocardial ischemia and infarction: anatomic and biochemical substrates for ischemic cell death and ventricular arrhythmias. Hum Pathol 18(5):462–475PubMedCrossRefGoogle Scholar
  54. 54.
    Buja LM, Entman ML (1998) Modes of myocardial cell injury and cell death in ischemic heart disease. Circulation 98(14):1355–1357PubMedCrossRefGoogle Scholar
  55. 55.
    Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92(2):139–150PubMedCrossRefGoogle Scholar
  56. 56.
    Wang H, Bei Y, Huang P, Zhou Q, Shi J, Sun Q, Zhong J, Li X, Kong X, Xiao J (2016) Inhibition of miR-155 protects against LPS-induced cardiac dysfunction and apoptosis in mice. Mol Ther Nucleic Acids 5(10):e374PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Vicencio JM, Yellon DM, Sivaraman V, Das D, Boi-Doku C, Arjun S, Zheng Y, Riquelme JA, Kearney J, Sharma V, Multhoff G, Hall AR, Davidson SM (2015) Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J Am Coll Cardiol 65(15):1525–1536PubMedCrossRefGoogle Scholar
  58. 58.
    Jakob P, Doerries C, Briand S, Mocharla P, Krankel N, Besler C, Mueller M, Manes C, Templin C, Baltes C, Rudin M, Adams H, Wolfrum M, Noll G, Ruschitzka F, Luscher TF, Landmesser U (2012) Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity. Circulation 126(25):2962–2975PubMedCrossRefGoogle Scholar
  59. 59.
    Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15(2):272–284PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN (2008) The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15(2):261–271PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Chen Y, Gorski DH (2008) Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111(3):1217–1226PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Taniguchi K, Kohno R, Ayada T, Kato R, Ichiyama K, Morisada T, Oike Y, Yonemitsu Y, Maehara Y, Yoshimura A (2007) Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Mol Cell Biol 27(12):4541–4550PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Rhoads K, Arderiu G, Charboneau A, Hansen SL, Hoffman W, Boudreau N (2005) A role for Hox A5 in regulating angiogenesis and vascular patterning. Lymphat Res Biol 3(4):240–252PubMedCrossRefGoogle Scholar
  64. 64.
    Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Phys Heart Circ Phys 285(2):H579–H588Google Scholar
  65. 65.
    Agrawal V, Gupta JK, Qureshi SS, Vishwakarma VK (2016) Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart. Indian Heart J 68(6):856–861PubMedCrossRefGoogle Scholar
  66. 66.
    Evans CW, Iyer KS, Hool LC (2016) The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart. Nanomedicine (Lond) 11(7):817–832CrossRefGoogle Scholar
  67. 67.
    Zhao W, Zheng XL, Zhao SP (2015) Exosome and its roles in cardiovascular diseases. Heart Fail Rev 20(3):337–348PubMedCrossRefGoogle Scholar
  68. 68.
    Buja LM, Vela D (2008) Cardiomyocyte death and renewal in the normal and diseased heart. Cardiovasc Pathol 17(6):349–374PubMedCrossRefGoogle Scholar
  69. 69.
    Radomski MW, Palmer RM, Moncada S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 2(8567):1057–1058PubMedCrossRefGoogle Scholar
  70. 70.
    Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87(4):1620–1624PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Xia Y, Zweier JL (1995) Substrate control of free radical generation from xanthine oxidase in the postischemic heart. J Biol Chem 270(32):18797–18803PubMedCrossRefGoogle Scholar
  72. 72.
    Loke KE, McConnell PI, Tuzman JM, Shesely EG, Smith CJ, Stackpole CJ, Thompson CI, Kaley G, Wolin MS, Hintze TH (1999) Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption. Circ Res 84(7):840–845PubMedCrossRefGoogle Scholar
  73. 73.
    Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, Levine B, Sadoshima J (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100(6):914–922PubMedCrossRefGoogle Scholar
  74. 74.
    Wang ZV, Rothermel BA, Hill JA (2010) Autophagy in hypertensive heart disease. J Biol Chem 285(12):8509–8514PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Khan M, Nickoloff E, Abramova T, Johnson J, Verma SK, Krishnamurthy P, Mackie AR, Vaughan E, Garikipati VN, Benedict C, Ramirez V, Lambers E, Ito A, Gao E, Misener S, Luongo T, Elrod J, Qin G, Houser SR, Koch WJ, Kishore R (2015) Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ Res 117(1):52–64PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Barile L, Moccetti T, Marbán E, Vassalli G (2017) Roles of exosomes in cardioprotection. Eur Heart J 38(18):1372–1379Google Scholar
  77. 77.
    Rana A, Goyal N, Ahlawat A, Jamwal S, Reddy BV, Sharma S (2015) Mechanisms involved in attenuated cardio-protective role of ischemic preconditioning in metabolic disorders. Perfusion 30(2):94–105PubMedCrossRefGoogle Scholar
  78. 78.
    Chen Q, Chen X, Han C, Wang Y, Huang T, Du Y, Dong Z (2016) FGF-2 transcriptionally down-regulates the expression of BNIP3L via PI3K/Akt/FoxO3a signaling and inhibits necrosis and mitochondrial dysfunction induced by high concentrations of hydrogen peroxide in H9c2 cells. Cell Physiol Biochem 40(6):1678–1691PubMedCrossRefGoogle Scholar
  79. 79.
    Pockley AG, Shepherd J, Corton JM (1998) Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol Investig 27(6):367–377CrossRefGoogle Scholar
  80. 80.
    Efthymiou CA, Mocanu MM, de Belleroche J, Wells DJ, Latchmann DS, Yellon DM (2004) Heat shock protein 27 protects the heart against myocardial infarction. Basic Res Cardiol 99(6):392–394PubMedCrossRefGoogle Scholar
  81. 81.
    Orogo AM, Gustafsson AB (2013) Cell death in the myocardium: my heart won’t go on. IUBMB Life 65(8):651–656PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Goldstein JA (1998) Right heart ischemia: pathophysiology, natural history, and clinical management. Prog Cardiovasc Dis 40(4):325–341PubMedCrossRefGoogle Scholar
  83. 83.
    Akodad M, Lattuca B, Nagot N, Georgescu V, Buisson M, Cristol JP, Leclercq F, Macia JC, Gervasoni R, Cung TT, Cade S, Cransac F, Labour J, Dupuy AM, Roubille F (2017) COLIN trial: value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response. Arch Cardiovasc Dis. doi: 10.1016/j.acvd.2016.10.004
  84. 84.
    Xanthopoulos A, Giamouzis G, Tryposkiadis K, Paraskevopoulou E, Paraskevopoulou P, Karagiannis G, Patsilinakos S, Parissis J, Farmakis D, Butler J, Skoularigis J, Triposkiadis F (2016) A simple score for early risk stratification in acute heart failure. Int J Cardiol 230:248–254PubMedCrossRefGoogle Scholar
  85. 85.
    Teng X, Chen L, Chen W, Yang J, Yang Z, Shen Z (2015) Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell Physiol Biochem 37(6):2415–2424PubMedCrossRefGoogle Scholar
  86. 86.
    Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P (2005) Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A 102(25):8966–8971PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M (2012) Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 60(4):290–299PubMedCrossRefGoogle Scholar
  88. 88.
    Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N, Ziemann M, Helbing T, El-Osta A, Jowett JB, Peter K (2012) Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res 93(4):633–644PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Rizzo M, Macario AJ, de Macario EC, Gouni-Berthold I, Berthold HK, Rini GB, Zummo G, Cappello F (2011) Heat shock protein-60 and risk for cardiovascular disease. Curr Pharm Des 17(33):3662–3668PubMedCrossRefGoogle Scholar
  90. 90.
    Kim SC, Stice JP, Chen L, Jung JS, Gupta S, Wang Y, Baumgarten G, Trial J, Knowlton AA (2009) Extracellular heat shock protein 60, cardiac myocytes, and apoptosis. Circ Res 105(12):1186–1195PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Zhang X, Wang X, Zhu H, Kranias EG, Tang Y, Peng T, Chang J, Fan GC (2012) Hsp20 functions as a novel cardiokine in promoting angiogenesis via activation of VEGFR2. PLoS One 7(3):e32765PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Cheng Y, Wang X, Yang J, Duan X, Yao Y, Shi X, Chen Z, Fan Z, Liu X, Qin S, Tang X, Zhang C (2012) A translational study of urine miRNAs in acute myocardial infarction. J Mol Cell Cardiol 53(5):668–676PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ Jr, Olson EN (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17(5):662–673PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Miyata S, Minobe W, Bristow MR, Leinwand LA (2000) Myosin heavy chain isoform expression in the failing and nonfailing human heart. Circ Res 86(4):386–390PubMedCrossRefGoogle Scholar
  95. 95.
    Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M, Kitamura T, Hamasaki T, Nanto S, Kawahara Y, Komuro I (2013) Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res 113(3):322–326PubMedCrossRefGoogle Scholar
  96. 96.
    Yun TJ, Lee JS, Shim D, Choi JH, Cheong C (2017) Isolation and characterization of aortic dendritic cells and lymphocytes in atherosclerosis. Methods Mol Biol 1559:419–437PubMedCrossRefGoogle Scholar
  97. 97.
    Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460(7256):705–710PubMedPubMedCentralGoogle Scholar
  98. 98.
    Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14(3):249–256PubMedCrossRefGoogle Scholar
  99. 99.
    Leroyer AS, Isobe H, Leseche G, Castier Y, Wassef M, Mallat Z, Binder BR, Tedgui A, Boulanger CM (2007) Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 49(7):772–777PubMedCrossRefGoogle Scholar
  100. 100.
    Rautou PE, Leroyer AS, Ramkhelawon B, Devue C, Duflaut D, Vion AC, Nalbone G, Castier Y, Leseche G, Lehoux S, Tedgui A, Boulanger CM (2011) Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res 108(3):335–343PubMedCrossRefGoogle Scholar
  101. 101.
    Niu C, Wang X, Zhao M, Cai T, Liu P, Li J, Willard B, Zu L, Zhou E, Li Y, Pan B, Yang F, Zheng L (2016) Macrophage foam cell-derived extracellular vesicles promote vascular smooth muscle cell migration and adhesion. J Am Heart Assoc 5(10). pii: e004099Google Scholar
  102. 102.
    Pironti G, Strachan RT, Abraham D, Mon-Wei Yu S, Chen M, Chen W, Hanada K, Mao L, Watson LJ, Rockman HA (2015) Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circulation 131(24):2120–2130PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Janiszewski M, Do Carmo AO, Pedro MA, Silva E, Knobel E, Laurindo FR (2004) Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: a novel vascular redox pathway. Crit Care Med 32(3):818–825PubMedCrossRefGoogle Scholar
  104. 104.
    Gambim MH, do Carmo Ade O, Marti L, Verissimo-Filho S, Lopes LR, Janiszewski M (2007) Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care 11(5):R107PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Wang Z, Ge J (2014) Managing hypercholesterolemia and preventing cardiovascular events in elderly and younger Chinese adults: focus on rosuvastatin. Clin Interv Aging 9:1–8PubMedGoogle Scholar
  106. 106.
    Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Murray CJ, Naghavi M (2014) Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the global burden of disease 2010 study. Circulation 129(14):1483–1492PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326–335PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Li TS, Cheng K, Malliaras K, Smith RR, Zhang Y, Sun B, Matsushita N, Blusztajn A, Terrovitis J, Kusuoka H, Marban L, Marban E (2012) Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol 59(10):942–953PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Matar AA, Chong JJ (2014) Stem cell therapy for cardiac dysfunction. Spring 3:440CrossRefGoogle Scholar
  110. 110.
    Shiba Y, Gomibuchi T, Seto T, Wada Y, Ichimura H, Tanaka Y, Ogasawara T, Okada K, Shiba N, Sakamoto K, Ido D, Shiina T, Ohkura M, Nakai J, Uno N, Kazuki Y, Oshimura M, Minami I, Ikeda U (2016) Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature 538(7625):388–391PubMedCrossRefGoogle Scholar
  111. 111.
    Nguyen BK, Maltais S, Perrault LP, Tanguay JF, Tardif JC, Stevens LM, Borie M, Harel F, Mansour S, Noiseux N (2010) Improved function and myocardial repair of infarcted heart by intracoronary injection of mesenchymal stem cell-derived growth factors. J Cardiovasc Transl Res 3(5):547–558PubMedCrossRefGoogle Scholar
  112. 112.
    Gaceb A, Martinez MC, Andriantsitohaina R (2014) Extracellular vesicles: new players in cardiovascular diseases. Int J Biochem Cell Biol 50:24–28PubMedCrossRefGoogle Scholar
  113. 113.
    Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25(2):371–379PubMedCrossRefGoogle Scholar
  114. 114.
    Zhang D, Lee H, Zhu Z, Minhas JK, Jin Y (2016) Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 312(1):L110–L121PubMedCrossRefGoogle Scholar
  115. 115.
    Lee Y, El Andaloussi S, Wood MJ (2012) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 21(R1):R125–R134PubMedCrossRefGoogle Scholar
  116. 116.
    El Andaloussi S, Lakhal S, Mager I, Wood MJ (2013) Exosomes for targeted siRNA delivery across biological barriers. Adv Drug Deliv Rev 65(3):391–397PubMedCrossRefGoogle Scholar
  117. 117.
    Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV, Batrakova EV (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Azevedo LC, Pedro MA, Laurindo FR (2007) Circulating microparticles as therapeutic targets in cardiovascular diseases. Recent Pat Cardiovasc Drug Discov 2(1):41–51PubMedCrossRefGoogle Scholar
  119. 119.
    Alvarez-Llamas G, de la Cuesta F, Barderas ME, Darde V, Padial LR, Vivanco F (2008) Recent advances in atherosclerosis-based proteomics: new biomarkers and a future perspective. Expert Rev Proteomics 5(5):679–691PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Yihua Bei
    • 1
  • Ting Chen
    • 2
  • Daniel Dumitru Banciu
    • 3
    • 4
  • Dragos Cretoiu
    • 5
    • 6
  • Junjie Xiao
    • 1
    Email author
  1. 1.Cardiac Regeneration and Ageing Lab, School of Life ScienceShanghai UniversityShanghaiChina
  2. 2.Laboratory for Advanced Interdisciplinary ResearchCenter for Personalized Medicine/Institutes of Translational Medicine, First Affiliated Hospital, Wenzhou Medical UniversityWenzhouChina
  3. 3.Research Beyond Limits SRLBucharestRomania
  4. 4.University of BucharestBucharestRomania
  5. 5.Victor Babes National Institute of PathologyBucharestRomania
  6. 6.Division of Cellular and Molecular Biology and HistologyCarol Davila University of Medicine and PharmacyBucharestRomania

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