Skip to main content
SpringerLink
Log in

Cardioprotective Effects of Exosomes and Their Potential Therapeutic Use

  • Chapter
  • First Online:
Exosomes in Cardiovascular Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 998))

Abstract

Exosomes are membrane-contained vesicles released by various types of cells both in animals and human. They contain microRNAs and proteins and can travel to target cells, affecting their functions. There are specific factors on the surface of every exosomes, making sure that they will be taken up by certain type of cells. With these features, exosomes have been recognized to be one of the fundamental “messengers” for cell-cell communication. Recently, increased interest has been raised in exosomes since they were discovered to play an unneglectable role in preserving cardiac function and cardiomyocyte repair during stress. The widely explored stem cell therapy for cardiomyopathy uncovered the contribution of exosomes. Here we summarized cardioprotective effects of exosomes and their potential therapeutic use.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee, Stroke Statistics Subcommittee (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133(4):e38–360

    Article  Google Scholar 

  2. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2014) Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129(3):399–410

    Article  PubMed  Google Scholar 

  3. Ieda M (2013) Heart development and regeneration via cellular interaction and reprogramming. Keio J Med 62(4):99–106

    Article  CAS  PubMed  Google Scholar 

  4. Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451(7181):937–942

    Article  CAS  PubMed  Google Scholar 

  5. Passier R, van Laake LW, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453(7193):322–329

    Article  CAS  PubMed  Google Scholar 

  6. Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nsair A, Schenke-Layland K, Van Handel B, Evseenko D, Kahn M, Zhao P, Mendelis J, Heydarkhan S, Awaji O, Vottler M, Geist S, Chyu J, Gago-Lopez N, Crooks GM, Plath K, Goldhaber J, Mikkola HK, MacLellan WR (2012) Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells. PLoS One 7(10):e45603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Miragoli M, Gaudesius G, Rohr S (2006) Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res 98(6):801–810

    Article  CAS  PubMed  Google Scholar 

  9. Civitarese RA, Kapus A, McCulloch CA, Connelly KA (2017) Role of integrins in mediating cardiac fibroblast-cardiomyocyte cross talk: a dynamic relationship in cardiac biology and pathophysiology. Basic Res Cardiol 112(1):6

    Article  PubMed  CAS  Google Scholar 

  10. Tirziu D, Giordano FJ, Simons M (2010) Cell communications in the heart. Circulation 122(9):928–937

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bell D, Campbell M, McAleer SF, Ferguson M, Donaghy L, Harbinson MT (2016) Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM(1) receptor. Peptides 76:1–13

    Article  CAS  PubMed  Google Scholar 

  12. Cervio E, Barile L, Moccetti T, Vassalli G (2015) Exosomes for intramyocardial intercellular communication. Stem Cells Int 2015:482171

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Zhang P, Su J, Mende U (2012) Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences. Am J Physiol Heart Circ Physiol 303(12):H1385–H1396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cherian S, Lopaschuk GD, Carvalho E (2012) Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. Am J Physiol Endocrinol Metab 303(8):937–949

    Article  CAS  Google Scholar 

  15. Tian Y, Morrisey EE (2012) Importance of myocyte-nonmyocyte interactions in cardiac development and disease. Circ Res 110(7):1023–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Doroudgar S, Glembotski CC (2011) The cardiokine story unfolds: ischemic stress-induced protein secretion in the heart. Trends Mol Med 17(4):207–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Kramer-Albers EM, Laitinen S, Lasser C, Lener T, Ligeti E, Line A, Lipps G, Llorente A, Lotvall J, Mancek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-’t Hoen EN, Nyman TA, O’Driscoll L, Olivan M, Oliveira C, Pallinger E, Del Portillo HA, Reventos J, Rigau M, Rohde E, Sammar M, Sanchez-Madrid F, Santarem N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066

    Article  PubMed  Google Scholar 

  18. Sluijter JP, Verhage V, Deddens JC, van den Akker F, Doevendans PA (2014) Microvesicles and exosomes for intracardiac communication. Cardiovasc Res 102(2):302–311

    Article  CAS  PubMed  Google Scholar 

  19. Chistiakov DA, Orekhov AN, Bobryshev YV (2016) Cardiac extracellular vesicles in normal and infarcted heart. Int J Mol Sci 17(1):63

    Article  PubMed Central  CAS  Google Scholar 

  20. Oliveira-Rodriguez M, Serrano-Pertierra E, Garcia AC, Lopez-Martin S, Yanez-Mo M, Cernuda-Morollon E, Blanco-Lopez MC (2017) Point-of-care detection of extracellular vesicles: sensitivity optimization and multiple-target detection. Biosens Bioelectron 87:38–45

    Article  CAS  PubMed  Google Scholar 

  21. Ciardiello C, Cavallini L, Spinelli C, Yang J, Reis-Sobreiro M, de Candia P, Minciacchi VR, Di Vizio D (2016) Focus on extracellular vesicles: new frontiers of cell-to-cell communication in cancer. Int J Mol Sci 17(2):175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kalra H, Drummen GP, Mathivanan S (2016) Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci 17(2):170

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Schorey JS, Cheng Y, Singh PP, Smith VL (2015) Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep 16(1):24–43

    Article  CAS  PubMed  Google Scholar 

  24. Crescitelli R, Lasser C, Szabo TG, Kittel A, Eldh M, Dianzani I, Buzas EI, Lotvall J (2013) Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles 2:20677

    Article  CAS  Google Scholar 

  25. Taylor DD, Gercel-Taylor C (2013) The origin, function, and diagnostic potential of RNA within extracellular vesicles present in human biological fluids. Front Genet 4:142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lazaro-Ibanez E, Sanz-Garcia A, Visakorpi T, Escobedo-Lucea C, Siljander P, Ayuso-Sacido A, Yliperttula M (2014) Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes. Prostate 74(14):1379–1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhu H, Fan GC (2011) Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am J Cardiovasc Dis 1(2):138–149

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Buzas EI, Gyorgy B, Nagy G, Falus A, Gay S (2014) Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol 10(6):356–364

    Article  CAS  PubMed  Google Scholar 

  29. Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123(Pt 10):1603–1611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Anderson HC, Garimella R, Tague SE (2005) The role of matrix vesicles in growth plate development and biomineralization. Front Biosci 10:822–837

    Article  CAS  PubMed  Google Scholar 

  31. Morel O, Toti F, Hugel B, Freyssinet JM (2004) Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 11(3):156–164

    Article  CAS  PubMed  Google Scholar 

  32. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10(5):619–624

    Article  CAS  PubMed  Google Scholar 

  33. 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):1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D (2016) Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 30(6):836–848

    Article  CAS  PubMed  Google Scholar 

  35. Zhang Z, Yang J, Yan W, Li Y, Shen Z, Asahara T (2016) Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. J Am Heart Assoc 5(1):e002856

    Google Scholar 

  36. Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M (2014) A comprehensive overview of exosomes as drug delivery vehicles—endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta 1846(1):75–87

    Google Scholar 

  37. Witwer KW, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-’t Hoen EN, Piper MG, Sivaraman S, Skog J, Thery C, Wauben MH, Hochberg F (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2. doi: 10.3402/jev.v2i0.20360

  38. Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820(7):940–948

    Article  CAS  PubMed  Google Scholar 

  39. Vrijsen KR, Maring JA, Chamuleau SA, Verhage V, Mol EA, Deddens JC, Metz CH, Lodder K, van Eeuwijk EC, van Dommelen SM, Doevendans PA, Smits AM, Goumans MJ, Sluijter JP (2016) Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Adv Healthc Mater 5(19):2555–2565

    Article  CAS  PubMed  Google Scholar 

  40. Batrakova EV, Kim MS (2015) Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release 219:396–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gross JC, Chaudhary V, Bartscherer K, Boutros M (2012) Active Wnt proteins are secreted on exosomes. Nat Cell Biol 14(10):1036–1045

    Article  CAS  PubMed  Google Scholar 

  42. Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA (2015) The fusion of two worlds: non-coding RNAs and extracellular vesicles—diagnostic and therapeutic implications (Review). Int J Oncol 46(1):17–27

    Article  CAS  PubMed  Google Scholar 

  43. Ailawadi S, Wang X, Gu H, Fan GC (2015) Pathologic function and therapeutic potential of exosomes in cardiovascular disease. Biochim Biophys Acta 1852(1):1–11

    Article  CAS  PubMed  Google Scholar 

  44. Barile L, Moccetti T, Marban E, Vassalli G (2017) Roles of exosomes in cardioprotection. Eur Heart J 38(18):1372–1379. doi:10.1093/eurheartj/ehw304

    PubMed  Google Scholar 

  45. 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):e34653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Villarroya-Beltri C, Baixauli F, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M (2014) Sorting it out: regulation of exosome loading. Semin Cancer Biol 28:3–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Anitei M, Wassmer T, Stange C, Hoflack B (2010) Bidirectional transport between the trans-Golgi network and the endosomal system. Mol Membr Biol 27(8):443–456

    Article  CAS  PubMed  Google Scholar 

  48. Akers JC, Gonda D, Kim R, Carter BS, Chen CC (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neuro-Oncol 113(1):1–11

    Article  Google Scholar 

  49. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14(7):677–685

    Article  CAS  PubMed  Google Scholar 

  50. Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Thery C, Raposo G (2013) Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci 126(Pt 24):5553–5565

    Article  CAS  PubMed  Google Scholar 

  51. 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):1484–1494

    Article  CAS  PubMed  Google Scholar 

  52. Hanson PI, Cashikar A (2012) Multivesicular body morphogenesis. Annu Rev Cell Dev Biol 28:337–362

    Article  CAS  PubMed  Google Scholar 

  53. Raiborg C, Stenmark H (2002) Hrs and endocytic sorting of ubiquitinated membrane proteins. Cell Struct Funct 27(6):403–408

    Article  CAS  PubMed  Google Scholar 

  54. Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3(2):283–289

    Article  CAS  PubMed  Google Scholar 

  55. Katzmann DJ, Babst M, Emr SD (2001) Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106(2):145–155

    Article  CAS  PubMed  Google Scholar 

  56. Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH (2009) Membrane scission by the ESCRT-III complex. Nature 458(7235):172–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kowal J, Tkach M, Thery C (2014) Biogenesis and secretion of exosomes. Curr Opin Cell Biol 29:116–125

    Article  CAS  PubMed  Google Scholar 

  58. Metcalf D, Isaacs AM (2010) The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. Biochem Soc Trans 38(6):1469–1473

    Article  CAS  PubMed  Google Scholar 

  59. de Gassart A, Geminard C, Fevrier B, Raposo G, Vidal M (2003) Lipid raft-associated protein sorting in exosomes. Blood 102(13):4336–4344

    Article  PubMed  CAS  Google Scholar 

  60. Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W (2003) Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 278(13):10963–10972

    Article  CAS  PubMed  Google Scholar 

  61. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319(5867):1244–1247

    Article  CAS  PubMed  Google Scholar 

  62. Kajimoto T, Okada T, Miya S, Zhang L, Nakamura S (2013) Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. Nat Commun 4:2712

    Article  PubMed  CAS  Google Scholar 

  63. Ghossoub R, Lembo F, Rubio A, Gaillard CB, Bouchet J, Vitale N, Slavik J, Machala M, Zimmermann P (2014) Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat Commun 5:3477

    Article  PubMed  CAS  Google Scholar 

  64. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30

    Article  CAS  PubMed  Google Scholar 

  65. Subra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M, De Medina P, Monsarrat B, Perret B, Silvente-Poirot S, Poirot M, Record M (2010) Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res 51(8):2105–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Emanueli C, Shearn AI, Angelini GD, Sahoo S (2015) Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vasc Pharmacol 71:24–30

    Article  CAS  Google Scholar 

  67. Gezer U, Ozgur E, Cetinkaya M, Isin M, Dalay N (2014) Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int 38(9):1076–1079

    CAS  PubMed  Google Scholar 

  68. Mathivanan S, Simpson RJ (2009) ExoCarta: a compendium of exosomal proteins and RNA. Proteomics 9(21):4997–5000

    Article  CAS  PubMed  Google Scholar 

  69. 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):654–659

    Article  CAS  PubMed  Google Scholar 

  70. Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S (2015) Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics 13(1):17–24

    Article  PubMed  PubMed Central  Google Scholar 

  71. Wang X, Huang W, Liu G, Cai W, Millard RW, Wang Y, Chang J, Peng T, Fan GC (2014) Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol 74:139–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107(14):6328–6333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. de Jong OG, Verhaar MC, Chen Y, Vader P, Gremmels H, Posthuma G, Schiffelers RM, Gucek M, van Balkom BW (2012) Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles 1. doi:10.3402/jev.v1i0.18396

  74. Khalyfa A, Gozal D (2014) Exosomal miRNAs as potential biomarkers of cardiovascular risk in children. J Transl Med 12:162

    Google Scholar 

  75. Li X, Liu M, Sun R, Zeng Y, Chen S, Zhang P (2016) Protective approaches against myocardial ischemia reperfusion injury. Exp Ther Med 12(6):3823–3829

    Article  PubMed  PubMed Central  Google Scholar 

  76. Callender T, Woodward M, Roth G, Farzadfar F, Lemarie JC, Gicquel S, Atherton J, Rahimzadeh S, Ghaziani M, Shaikh M, Bennett D, Patel A, Lam CS, Sliwa K, Barretto A, Siswanto BB, Diaz A, Herpin D, Krum H, Eliasz T, Forbes A, Kiszely A, Khosla R, Petrinic T, Praveen D, Shrivastava R, Xin D, MacMahon S, McMurray J, Rahimi K (2014) Heart failure care in low- and middle-income countries: a systematic review and meta-analysis. PLoS Med 11(8):e1001699

    Article  PubMed  PubMed Central  Google Scholar 

  77. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, DK MG, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2015) Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131(4):e29–322

    Article  PubMed  Google Scholar 

  78. Yuan MJ, Maghsoudi T, Wang T (2016) Exosomes mediate the intercellular communication after myocardial infarction. Int J Med Sci 13(2):113–116

    Article  PubMed  PubMed Central  Google Scholar 

  79. Reddy K, Khaliq A, Henning RJ (2015) Recent advances in the diagnosis and treatment of acute myocardial infarction. World J Cardiol 7(5):243–276

    Article  PubMed  PubMed Central  Google Scholar 

  80. Huebener P, Abou-Khamis T, Zymek P, Bujak M, Ying X, Chatila K, Haudek S, Thakker G, Frangogiannis NG (2008) CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol 180(4):2625–2633

    Article  CAS  PubMed  Google Scholar 

  81. 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, Mairbaurl H, Nawroth PP, Remppis A, Katus HA, Bierhaus A (2008) High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation 117(25):3216–3226

    Article  CAS  PubMed  Google Scholar 

  82. Lugrin J, Parapanov R, Rosenblatt-Velin N, Rignault-Clerc S, Feihl F, Waeber B, Muller O, Vergely C, Zeller M, Tardivel A, Schneider P, Pacher P, Liaudet L (2015) Cutting edge: IL-1alpha is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction. J Immunol 194(2):499–503

    Article  CAS  PubMed  Google Scholar 

  83. Chen C, Feng Y, Zou L, Wang L, Chen HH, Cai JY, Xu JM, Sosnovik DE, Chao W (2014) Role of extracellular RNA and TLR3-Trif signaling in myocardial ischemia-reperfusion injury. J Am Heart Assoc 3(1):e000683

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Frangogiannis NG (2014) The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities. J Cardiovasc Pharmacol 63(3):185–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 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):e0154274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Lindblom RP, Lytsy B, Sandstrom C, Ligata N, Larsson B, Ransjo U, Swenne CL (2015) Outcomes following the implementation of a quality control campaign to decrease sternal wound infections after coronary artery by-pass grafting. BMC Cardiovasc Disord 15:154

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Fortuna D, Nicolini F, Guastaroba P, De Palma R, Di Bartolomeo S, Saia F, Pacini D, Grilli R, RERIC (Regional Registry of Cardiac Surgery), REAL (Regional Registry of Coronary Angioplasties) Investigators (2013) Coronary artery bypass grafting vs percutaneous coronary intervention in a ‘real-world’ setting: a comparative effectiveness study based on propensity score-matched cohorts. Eur J Cardiothorac Surg 44(1):e16–e24

    Article  PubMed  Google Scholar 

  88. Ferguson TB Jr (2016) Physiology of in-situ arterial revascularization in coronary artery bypass grafting: preoperative, intraoperative and postoperative factors and influences. World J Cardiol 8(11):623–637

    Article  PubMed  Google Scholar 

  89. Ghista DN, Kabinejadian F (2013) Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical engineering review. Biomed Eng Online 12:129

    Article  PubMed  PubMed Central  Google Scholar 

  90. Rihal CS, Raco DL, Gersh BJ, Yusuf S (2003) Indications for coronary artery bypass surgery and percutaneous coronary intervention in chronic stable angina: review of the evidence and methodological considerations. Circulation 108(20):2439–2445

    Article  PubMed  Google Scholar 

  91. Ma TK, Kam KK, Yan BP, Lam YY (2010) Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br J Pharmacol 160(6):1273–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Rywik TM (2011) [Summary of the article: Zannad F, McMurray JJV, Krum H et al.; for the EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med, 2011; 364: 11-21]. Kardiol Pol 69(6):631–632

    Google Scholar 

  93. Gring CN, Francis GS (2004) A hard look at angiotensin receptor blockers in heart failure. J Am Coll Cardiol 44(9):1841–1846

    Article  CAS  PubMed  Google Scholar 

  94. Yamaguchi T, Izumi Y, Nakamura Y, Yamazaki T, Shiota M, Sano S, Tanaka M, Osada-Oka M, Shimada K, Miura K, Yoshiyama M, Iwao H (2015) Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction. Int J Cardiol 178:239–246

    Article  PubMed  Google Scholar 

  95. Kleinbongard P, Skyschally A, Heusch G (2017) Cardioprotection by remote ischemic conditioning and its signal transduction. Pflugers Arch 469(2):159–181

    Article  CAS  PubMed  Google Scholar 

  96. Elbadawi A, Ha LD, Abuzaid AS, Crimi G, Azzouz MS (2017) Meta-analysis of randomized trials on remote ischemic conditioning during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Am J Cardiol 119(6):832–838

    Article  PubMed  Google Scholar 

  97. Foglio E, Puddighinu G, Fasanaro P, D’Arcangelo D, Perrone GA, Mocini D, Campanella C, Coppola L, Logozzi M, Azzarito T, Marzoli F, Fais S, Pieroni L, Marzano V, Germani A, Capogrossi MC, Russo MA, Limana F (2015) Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis. Int J Cardiol 197:333–347

    Article  PubMed  Google Scholar 

  98. 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):52–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. 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):2415–2424

    Article  CAS  PubMed  Google Scholar 

  100. Yu B, Gong M, Wang Y, Millard RW, Pasha Z, Yang Y, Ashraf M, Xu M (2013) Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles. PLoS One 8(8):e73304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Li H, Zuo S, He Z, Yang Y, Pasha Z, Wang Y, Xu M (2010) Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival. Am J Physiol Heart Circ Physiol 299(6):H1772–H1781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Yu B, Kim HW, Gong M, Wang J, Millard RW, Wang Y, Ashraf M, Xu M (2015) Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. Int J Cardiol 182:349–360

    Article  PubMed  Google Scholar 

  103. Liu H, Gao W, Yuan J, Wu C, Yao K, Zhang L, Ma L, Zhu J, Zou Y, Ge J (2016) Exosomes derived from dendritic cells improve cardiac function via activation of CD4(+) T lymphocytes after myocardial infarction. J Mol Cell Cardiol 91:123–133

    Article  CAS  PubMed  Google Scholar 

  104. Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T (2012) Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth 16(3):123–132

    Article  PubMed  PubMed Central  Google Scholar 

  105. Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74(5):1124–1136

    Article  CAS  PubMed  Google Scholar 

  107. Ueno K, Samura M, Nakamura T, Tanaka Y, Takeuchi Y, Kawamura D, Takahashi M, Hosoyama T, Morikage N, Hamano K (2016) Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p. Sci Rep 6:36758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Giricz Z, Varga ZV, Baranyai T, Sipos P, Paloczi K, Kittel A, Buzas EI, Ferdinandy P (2014) Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles. J Mol Cell Cardiol 68:75–78

    Article  CAS  PubMed  Google Scholar 

  109. Li J, Rohailla S, Gelber N, Rutka J, Sabah N, Gladstone RA, Wei C, Hu P, Kharbanda RK, Redington AN (2014) MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Res Cardiol 109(5):423

    Article  PubMed  CAS  Google Scholar 

  110. 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):1525–1536

    Article  CAS  PubMed  Google Scholar 

  111. 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):566–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK (2010) Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 4(3):214–222

    Article  CAS  PubMed  Google Scholar 

  113. Tang YL, Zhu W, Cheng M, Chen L, Zhang J, Sun T, Kishore R, Phillips MI, Losordo DW, Qin G (2009) Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 104(10):1209–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Shengguang Ding, Jingying Zhang and Qiying Dai contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China

    Shengguang Ding, Haitao Huang, Yiming Xu & Chongjun Zhong

  2. Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China

    Jingying Zhang

  3. Metrowest Medical Center, Framingham, MA, 01702, USA

    Qiying Dai

  4. Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Qiying Dai

  5. Department of Rehabilitation Medicine, Second Medical School of Nanjing University of Chinese Medicine, Nanjing, 210001, China

    Mengfei Zhao

Authors
  1. Shengguang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiying Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengfei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haitao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yiming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chongjun Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chongjun Zhong .

Editor information

Editors and Affiliations

  1. Shanghai University , Shanghai, China

    Junjie Xiao

  2. Victor Babeş National Institute of Patho , Bucharest, Romania

    Sanda Cretoiu

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Ding, S. et al. (2017). Cardioprotective Effects of Exosomes and Their Potential Therapeutic Use. In: Xiao, J., Cretoiu, S. (eds) Exosomes in Cardiovascular Diseases. Advances in Experimental Medicine and Biology, vol 998. Springer, Singapore. https://doi.org/10.1007/978-981-10-4397-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation