Exosomes as Diagnostic Biomarkers in Cardiovascular Diseases

  • Felix JansenEmail author
  • Qian Li
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 998)


Exosomes play important roles in the development and progression of cardiovascular diseases by modulating intercellular communication. Contents and quantities of exosomes are variable under different pathological cardiovascular conditions. Based on these concepts, exosomes have been proposed as novel diagnostic biomarkers in cardiovascular diseases. However, many issues related with clinically applicable biomarkers remain unresolved. Within this chapter, we discuss the potential value, but also the current challenges using exosome numbers and contents as diagnostic and prognostic biomarker in diverse cardiovascular pathologies.


Exosomes Biomarkers Cardiovascular diseases 


  1. 1.
    Simons M, Raposo G (2009) Exosomes—vesicular carriers for intercellular communication. Curr Opin Cell Biol 21(4):575–581CrossRefPubMedGoogle Scholar
  2. 2.
    Das S, Halushka MK (2015) Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc Pathol 24(4):199–206CrossRefPubMedGoogle Scholar
  3. 3.
    Amabile N, Rautou PE, Tedgui A, Boulanger CM (2010) Microparticles: key protagonists in cardiovascular disorders. Semin Thromb Hemost 36(8):907–916CrossRefPubMedGoogle Scholar
  4. 4.
    Owens AP III, Mackman N (2011) Microparticles in hemostasis and thrombosis. Circ Res 108(10):1284–1297CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Khalyfa A, Gozal D (2014) Exosomal miRNAs as potential biomarkers of cardiovascular risk in children. J Transl Med 12:162CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pfeifer P, Werner N, Jansen F (2015) Role and function of microRNAs in extracellular vesicles in cardiovascular biology. Biomed Res Int 2015:161393CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Loyer X, Vion AC, Tedgui A, Boulanger CM (2014) Microvesicles as cell-cell messengers in cardiovascular diseases. Circ Res 114(2):345–353CrossRefPubMedGoogle Scholar
  8. 8.
    Izarra A, Moscoso I, Levent E, Canon S, Cerrada I, Diez-Juan A, Blanca V, Nunez-Gil IJ, Valiente I, Ruiz-Sauri A, Sepulveda P, Tiburcy M, Zimmermann WH, Bernad A (2014) miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Rep 3(6):1029–1042CrossRefGoogle Scholar
  9. 9.
    Lawson C, Vicencio JM, Yellon DM, Davidson SM (2016) Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J Endocrinol 228(2):R57–R71CrossRefPubMedGoogle Scholar
  10. 10.
    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):566–571CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Boon RA, Hergenreider E, Dimmeler S (2012) Atheroprotective mechanisms of shear stress-regulated microRNAs. Thromb Haemost 108(4):616–620CrossRefPubMedGoogle Scholar
  12. 12.
    Thery C, Duban L, Segura E, Veron P, Lantz O, Amigorena S (2002) Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol 3(12):1156–1162CrossRefPubMedGoogle Scholar
  13. 13.
    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
  14. 14.
    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):e34653CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Iaconetti C, Sorrentino S, De Rosa S, Indolfi C (2016) Exosomal miRNAs in heart disease. Physiology (Bethesda) 31(1):16–24Google Scholar
  16. 16.
    Deddens JC, Vrijsen KR, Colijn JM, Oerlemans MI, Metz CH, van der Vlist EJ, Nolte-’t Hoen EN, den Ouden K, Jansen Of Lorkeers SJ, van der Spoel TI, Koudstaal S, Arkesteijn GJ, Wauben MH, van Laake LW, Doevendans PA, Chamuleau SA, Sluijter JP (2016) Circulating extracellular vesicles contain miRNAs and are released as early biomarkers for cardiac injury. J Cardiovasc Transl Res 9(4):291–301CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Stremersch S, De Smedt SC, Raemdonck K (2016) Therapeutic and diagnostic applications of extracellular vesicles. J Control Release 244(Pt B):167–183CrossRefPubMedGoogle Scholar
  18. 18.
    Yellon DM, Davidson SM (2014) Exosomes: nanoparticles involved in cardioprotection? Circ Res 114(2):325–332CrossRefPubMedGoogle Scholar
  19. 19.
    Tual-Chalot S, Leonetti D, Andriantsitohaina R, Martinez MC (2011) Microvesicles: intercellular vectors of biological messages. Mol Interv 11(2):88–94CrossRefPubMedGoogle Scholar
  20. 20.
    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):654–659CrossRefPubMedGoogle Scholar
  21. 21.
    Dear JW, Street JM, Bailey MA (2013) Urinary exosomes: a reservoir for biomarker discovery and potential mediators of intrarenal signalling. Proteomics 13(10–11):1572–1580CrossRefPubMedGoogle Scholar
  22. 22.
    Keller S, Sanderson MP, Stoeck A, Altevogt P (2006) Exosomes: from biogenesis and secretion to biological function. Immunol Lett 107(2):102–108CrossRefPubMedGoogle Scholar
  23. 23.
    Gallo A, Tandon M, Alevizos I, Illei GG (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7(3):e30679CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF, Tewari M (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108(12):5003–5008CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Li C, Pei F, Zhu X, Duan DD, Zeng C (2012) Circulating microRNAs as novel and sensitive biomarkers of acute myocardial infarction. Clin Biochem 45(10–11):727–732CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    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):446–454CrossRefPubMedGoogle Scholar
  27. 27.
    D’Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, Rubino M, Carena MC, Spazzafumo L, De Simone M, Micheli B, Biglioli P, Achilli F, Martelli F, Maggiolini S, Marenzi G, Pompilio G, Capogrossi MC (2010) Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 31(22):2765–2773CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sayed AS, Xia K, Yang TL, Peng J (2013) Circulating microRNAs: a potential role in diagnosis and prognosis of acute myocardial infarction. Dis Markers 35(5):561–566CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Divakaran V, Mann DL (2008) The emerging role of microRNAs in cardiac remodeling and heart failure. Circ Res 103(10):1072–1083CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Small EM, Olson EN (2011) Pervasive roles of microRNAs in cardiovascular biology. Nature 469(7330):336–342CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    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):322–326CrossRefPubMedGoogle Scholar
  32. 32.
    Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen NQ, Scherr M, Castermans K, Malvaux L, Lambert V, Thiry M, Sliwa K, Noel A, Martial JA, Hilfiker-Kleiner D, Struman I (2013) MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Investig 123(5):2143–2154CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, Sinning JM, Vasa-Nicotera M, Nickenig G, Werner N (2014) MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc 3(6):e001249CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Natarelli L, Schober A (2015) MicroRNAs and the response to injury in atherosclerosis. Hamostaseologie 35(2):142–150CrossRefPubMedGoogle Scholar
  35. 35.
    Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O (2012) Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 14(2):147–154CrossRefPubMedGoogle Scholar
  36. 36.
    Jayachandran M, Litwiller RD, Lahr BD, Bailey KR, Owen WG, Mulvagh SL, Heit JA, Hodis HN, Harman SM, Miller VM (2011) Alterations in platelet function and cell-derived microvesicles in recently menopausal women: relationship to metabolic syndrome and atherogenic risk. J Cardiovasc Transl Res 4(6):811–822CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Diamant M, Nieuwland R, Pablo RF, Sturk A, Smit JW, Radder JK (2002) Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 106(19):2442–2447CrossRefPubMedGoogle Scholar
  38. 38.
    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 74:139–150CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Karolina DS, Armugam A, Tavintharan S, Wong MT, Lim SC, Sum CF, Jeyaseelan K (2011) MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PLoS One 6(8):e22839CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, Zhao J, Zhao L (2011) Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol 48(1):61–69CrossRefPubMedGoogle Scholar
  41. 41.
    Tijsen AJ, Pinto YM, Creemers EE (2012) Circulating microRNAs as diagnostic biomarkers for cardiovascular diseases. Am J Physiol Heart Circ Physiol 303(9):H1085–H1095CrossRefPubMedGoogle Scholar
  42. 42.
    Jansen F, Yang X, Hoelscher M, Cattelan A, Schmitz T, Proebsting S, Wenzel D, Vosen S, Franklin BS, Fleischmann BK, Nickenig G, Werner N (2013) Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation 128(18):2026–2038CrossRefPubMedGoogle Scholar
  43. 43.
    Jansen F, Wang H, Przybilla D, Franklin BS, Dolf A, Pfeifer P, Schmitz T, Flender A, Endl E, Nickenig G, Werner N (2016) Vascular endothelial microparticles-incorporated microRNAs are altered in patients with diabetes mellitus. Cardiovasc Diabetol 15:49CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    O’Neill S, O’Driscoll L (2015) Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 16(1):1–12CrossRefPubMedGoogle Scholar
  45. 45.
    O’Neill S, Bohl M, Gregersen S, Hermansen K, O’Driscoll L (2016) Blood-based biomarkers for metabolic syndrome. Trends Endocrinol Metab 27(6):363–374CrossRefPubMedGoogle Scholar
  46. 46.
    Rottiers V, Naar AM (2012) MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol 13(4):239–250CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Pek SL, Wong MT, Lim SC, Sum CF, Jeyaseelan K (2012) Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97(12):E2271–E2276CrossRefPubMedGoogle Scholar
  48. 48.
    Yu X, Deng L, Wang D, Li N, Chen X, Cheng X, Yuan J, Gao X, Liao M, Wang M, Liao Y (2012) Mechanism of TNF-alpha autocrine effects in hypoxic cardiomyocytes: initiated by hypoxia inducible factor 1alpha, presented by exosomes. J Mol Cell Cardiol 53(6):848–857CrossRefPubMedGoogle Scholar
  49. 49.
    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):2120–2130CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    de Hoog VC, Timmers L, Schoneveld AH, Wang JW, van de Weg SM, Sze SK, van Keulen JK, Hoes AW, den Ruijter HM, de Kleijn DP, Mosterd A (2013) Serum extracellular vesicle protein levels are associated with acute coronary syndrome. Eur Heart J Acute Cardiovasc Care 2(1):53–60CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Cheow ES, Cheng WC, Lee CN, de Kleijn D, Sorokin V, Sze SK (2016) Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic (MI) injury. Mol Cell Proteomics 15(8):2628–2640CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Aswad H, Forterre A, Wiklander OP, Vial G, Danty-Berger E, Jalabert A, Lamaziere A, Meugnier E, Pesenti S, Ott C, Chikh K, El-Andaloussi S, Vidal H, Lefai E, Rieusset J, Rome S (2014) Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice. Diabetologia 57(10):2155–2164CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Medizinische Klinik und Poliklinik IIUniversitätsklinikum BonnBonnGermany

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