Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets

Abstract

microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-cell communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.

Keywords

microRNA / cardiovascular disease / biomarkers / therapeutic target

References

[1] Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell2004; 116(2): 281–297

[2] Ambros V. The functions of animal microRNAs. Nature2004; 431(7006): 350–355

[3] Papageorgiou N, Tousoulis D, Androulakis E, Siasos G, Briasoulis A, Vogiatzi G, Kampoli AM, Tsiamis E, Tentolouris C, Stefanadis C. The role of microRNAs in cardiovascular disease. Curr Med Chem2012; 19(16): 2605–2610

[4] Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J2002; 21(17): 4663–4670

[5] Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA2004; 10(12): 1957–1966

[6] Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev2003; 17(24): 3011–3016

[7] Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science2004; 303(5654): 95–98

[8] Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA2004; 10(2): 185–191

[9] Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol2009; 10(2): 126–139

[10] Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell2006; 125(6): 1111–1124

[11] Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol2007; 17(3): 118–126

[12] Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature2010; 466(7308): 835–840

[13] Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res2011; 39(Database): D152–D157

[14] Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell2005; 120(1): 21–24

[15] Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell2005; 120(1): 15–20

[16] Hata A. Functions of microRNAs in cardiovascular biology and disease. Annu Rev Physiol2013; 75(1): 69–93

[17] Quiat D, Olson EN. MicroRNAs in cardiovascular disease: from pathogenesis to prevention and treatment. J Clin Invest2013; 123(1): 11–18

[18] Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation2008; 117(4): e25–e146

[19] Charakida M, Tousoulis D, Stefanadis C. Early atherosclerosis in childhood: diagnostic approaches and therapeutic strategies. Int J Cardiol2006; 109(2): 152–159

[20] Ono K, Kuwabara Y, Han J. MicroRNAs and cardiovascular diseases. FEBS J2011; 278(10): 1619–1633

[21] Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation2010; 121(8): 1022–1032

[22] van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov2012; 11(11): 860–872

[23] van Rooij E, Marshall WS, Olson EN. Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res2008; 103(9): 919–928

[24] Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res2012; 110(3): 483–495

[25] Fichtlscherer S, Zeiher AM, Dimmeler S, Sessa WC. Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol2011; 31(11): 2383–2390

[26] Li WY, Jin J, Chen J, Guo Y, Tang J, Tan S. Circulating microRNAs as potential non-invasive biomarkers for the early detection of hypertension-related stroke. J Hum Hypertens2014; 28(5): 288–291

[27] Marfella R, Di Filippo C, Potenza N, Sardu C, Rizzo MR, Siniscalchi M, Musacchio E, Barbieri M, Mauro C, Mosca N, Solimene F, Mottola MT, Russo A, Rossi F, Paolisso G, D’Amico M. Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders. Eur J Heart Fail2013; 15(11): 1277–1288

[28] Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol2008; 141(5): 672–675

[29] Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA2008; 105(30): 10513–10518

[30] Tsui NB, Ng EK, Lo YM. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin Chem2002; 48(10): 1647–1653

[31] El-Hefnawy T, Raja S, Kelly L, Bigbee WL, Kirkwood JM, Luketich JD, Godfrey TE. Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem2004; 50(3): 564–573

[32] Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res2008; 18(10): 997–1006

[33] Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem2010; 285(23): 17442–17452

[34] Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol2007; 9(6): 654–659

[35] Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia2006; 20(5): 847–856

[36] Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol2002; 2(8): 569–579

[37] Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int2010; 78(9): 838–848

[38] Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS ONE2010; 5(10): e13515

[39] Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem2013; 288: 10849–10859

[40] Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol2012; 14(3): 249–256

[41] Hemler ME. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol2003; 19(1): 397–422

[42] Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, Lochnit G, Preissner KT, Zöller M. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res2010; 70(4): 1668–1678

[43] Rana S, Yue S, Stadel D, Zöller M. Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol2012; 44(9): 1574–1584

[44] van den Boorn JG, Dassler J, Coch C, Schlee M, Hartmann G. Exosomes as nucleic acid nanocarriers. Adv Drug Deliv Rev2013; 65(3): 331–335

[45] Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia2006; 20(9): 1487–1495

[46] Mack M, Kleinschmidt A, Brühl H, Klier C, Nelson PJ, Cihak J, Plachý J, Stangassinger M, Erfle V, Schlöndorff D. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med2000; 6(7): 769–775

[47] Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C. Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci2010; 123(10): 1603–1611

[48] Prokopi M, Pula G, Mayr U, Devue C, Gallagher J, Xiao Q, Boulanger CM, Westwood N, Urbich C, Willeit J, Steiner M, Breuss J, Xu Q, Kiechl S, Mayr M. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood2009; 114(3): 723–732

[49] Mause SF, Ritzel E, Liehn EA, Hristov M, Bidzhekov K, Müller-Newen G, Soehnlein O, Weber C. Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation2010; 122(5): 495–506

[50] Zampetaki A, Willeit P, Drozdov I, Kiechl S, Mayr M. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res2012; 93(4): 555–562

[51] Köppler B, Cohen C, Schlöndorff D, Mack M. Differential mechanisms of microparticle transfer toB cells and monocytes: anti-inflammatory propertiesof microparticles. Eur J Immunol2006; 36(3): 648–660

[52] Pula G, Perera S, Prokopi M, Sidibe A, Boulanger CM, Mayr M. Proteomic analysis of secretory proteins and vesicles in vascular research. Proteomics Clin Appl2008; 2(6): 882–891

[53] Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, Sun F, Lu J, Yin Y, Cai X, Sun Q, Wang K, Ba Y, Wang Q, Wang D, Yang J, Liu P, Xu T, Yan Q, Zhang J, Zen K, Zhang CY. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell2010; 39(1): 133–144

[54] Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS ONE2010; 5(7): e11803

[55] Leroyer AS, Ebrahimian TG, Cochain C, Récalde A, Blanc-Brude O, Mees B, Vilar J, Tedgui A, Levy BI, Chimini G, Boulanger CM, Silvestre JS. Microparticles from ischemic muscle promotes postnatal vasculogenesis. Circulation2009; 119(21): 2808–2817

[56] VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res2003; 59(2): 277–287

[57] Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N, Ziemann M, Helbing T, El-Osta A, Jowett JB, Peter K. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res2012; 93(4): 633–644

[58] Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res2010; 107(9): 1047–1057

[59] Huber J, Vales A, Mitulovic G, Blumer M, Schmid R, Witztum JL, Binder BR, Leitinger N. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler Thromb Vasc Biol2002; 22(1): 101–107

[60] Beyer C, Pisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseases. Nat Rev Rheumatol2010; 6(1): 21–29

[61] Holmgren L, Bergsmedh A, Spetz AL. Horizontal transfer of DNA by the uptake of apoptotic bodies. Vox Sang2002; 83(Suppl 1): 305–306

[62] Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Köppel T, Jahantigh MN, Lutgens E, Wang S, Olson EN, Schober A, Weber C. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal2009; 2(100): ra81

[63] Janas T, Janas T, Yarus M. Specific RNA binding to ordered phospholipid bilayers. Nucleic Acids Res2006; 34(7): 2128–2136

[64] Kim SI, Shin D, Choi TH, Lee JC, Cheon GJ, Kim KY, Park M, Kim M. Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. Mol Ther2007; 15(6): 1145–1152

[65] Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol2011; 13(4): 423–433

[66] 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. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA2011; 108(12): 5003–5008

[67] Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res2011; 39(16): 7223–7233

[68] Turchinovich A, Burwinkel B. Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma. RNA Biol2012; 9(8): 1066–1075

[69] Wang K, Zhang S, Weber J, Baxter D, Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res2010; 38(20): 7248–7259

[70] 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. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J2010; 31(22): 2765–2773

[71] Oerlemans MI, Mosterd A, Dekker MS, de Vrey EA, van Mil A, Pasterkamp G, Doevendans PA, Hoes AW, Sluijter JP. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO Mol Med2012; 4(11): 1176–1185

[72] Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J2010; 31(6): 659–666

[73] Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, Nonogi H, Iwai N. Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem2010; 56(7): 1183–1185

[74] Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res2010; 106(6): 1035–1039

[75] Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Röxe T, Müller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res2010; 107(5): 677–684

[76] Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation2011; 124(2): 175–184

[77] Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet2010; 3(6): 499–506

[78] White HD, Chew DP. Acute myocardial infarction. Lancet2008; 372(9638): 570–584

[79] van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science2007; 316(5824): 575–579

[80] Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem2009; 55(11): 1944–1949

[81] Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, Dong X, Qin S, Zhang C. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond)2010; 119(2): 87–95

[82] Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, Li K, Yu B, Li Z, Wang R, Wang L, Li Q, Wang N, Shan H, Li Z, Yang B. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun2010; 391(1): 73–77

[83] De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM. Transcoronary concentration gradients of circulating microRNAs. Circulation2011; 124(18): 1936–1944

[84] 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. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet2011; 4(4): 446–454

[85] Wang F, Long G, Zhao C, Li H, Chaugai S, Wang Y, Chen C, Wang DW. Plasma microRNA-133a is a new marker for both acute myocardial infarction and underlying coronary artery stenosis. J Transl Med2013; 11: 222

[86] Boštjančič E, Zidar N, Štajer D, Glavač D. MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology2010; 115(3): 163–169

[87] van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ Jr, Olson EN. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell2009; 17(5): 662–673

[88] Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet2006; 38(2): 228–233

[89] Long G, Wang F, Duan Q, Chen F, Yang S, Gong W, Wang Y, Chen C, Wang DW. Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction. Int J Biol Sci2012; 8(6): 811–818

[90] Long G, Wang F, Duan Q, Yang S, Chen F, Gong W, Yang X, Wang Y, Chen C, Wang DW. Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PLoS ONE2012; 7(12): e50926

[91] Wang F, Long G, Zhao C, Li H, Chaugai S, Wang Y, Chen C, Wang DW. Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction. PLoS ONE2014; 9(9): e105734

[92] 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. Prospective study on circulating microRNAs and risk of myocardial infarction. J Am Coll Cardiol2012; 60(4): 290–299

[93] Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J2011; 75(2): 336–340

[94] Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res2010; 107(6): 810–817

[95] Hoekstra M, van der Lans CA, Halvorsen B, Gullestad L, Kuiper J, Aukrust P, van Berkel TJ, Biessen EA. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochem Biophys Res Commun2010; 394(3): 792–797

[96] Yang LX, Liu G, Zhu GF, Liu H, Guo RW, Qi F, Zou JH. MicroRNA-155 inhibits angiotensin II-induced vascular smooth muscle cell proliferation. J Renin Angiotensin Aldosterone Syst2014; 15: 109–116

[97] Ceolotto G, Papparella I, Bortoluzzi A, Strapazzon G, Ragazzo F, Bratti P, Fabricio AS, Squarcina E, Gion M, Palatini P, Semplicini A. Interplay between miR-155, AT1R A1166C polymorphism, and AT1R expression in young untreated hypertensives. Am J Hypertens2011; 24(2): 241–246

[98] Gan CS, Wang CW, Tan KS. Circulatory microRNA-145 expression is increased in cerebral ischemia. Genet Mol Res2012; 11(1): 147–152

[99] Long G, Wang F, Li H, Yin Z, Sandip C, Lou Y, Wang Y, Chen C, Wang DW. Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol2013; 13(1): 178

[100] Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol2008; 10(12): 1470–1476

[101] 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. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest2013; 123(5): 2143–2154

[102] Yang Y, Rodriguez JE, Kitsis RN. A microRNA links prolactin to peripartum cardiomyopathy. J Clin Invest2013; 123(5): 1925–1927

[103] Wang X, Huang W, Liu G, Cai W, Millard RW, Wang Y, Chang J, Peng T, Fan GC. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol2014; 74: 139–150

[104] Iguchi H, Kosaka N, Ochiya T. Secretory microRNAs as a versatile communication tool. Commun Integr Biol2010; 3(5): 478–481

[105] Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T, Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA2010; 107(14): 6328–6333

[106] Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, Milosevic J, Tkacheva OA, Divito SJ, Jordan R, Lyons-Weiler J, Watkins SC, Morelli AE. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood2012; 119(3): 756–766

[107] McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem2011; 57(6): 833–840

[108] van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci USA2006; 103(48): 18255–18260

[109] Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation2007; 116(3): 258–267

[110] Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature2008; 456(7224): 980–984

[111] van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA2008; 105(35): 13027–13032

[112] Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell2008; 15(2): 261–271

[113] Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR. Treatment of HCV infection by targeting microRNA. N Engl J Med2013; 368(18): 1685–1694

[114] Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM, Stack C, Latimer PA, Olson EN, van Rooij E. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation2011; 124(14): 1537–1547

[115] Grueter CE, van Rooij E, Johnson BA, DeLeon SM, Sutherland LB, Qi X, Gautron L, Elmquist JK, Bassel-Duby R, Olson EN. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell2012; 149(3): 671–683

[116] Hullinger TG, Montgomery RL, Seto AG, Dickinson BA, Semus HM, Lynch JM, Dalby CM, Robinson K, Stack C, Latimer PA, Hare JM, Olson EN, van Rooij E. Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res2012; 110(1): 71–81

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