Role of MicroRNAs in Diagnosis, Prognosis, and Treatment of Acute Heart Failure: Ambassadors from Intracellular Zone

  • Seyyed-Reza Sadat-Ebrahimi 1. Cardiovascular Research Center, Madani Heart Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Naser Aslanabadi 1. Cardiovascular Research Center, Madani Heart Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords: Heart Failure; MicroRNA; Diagnosis; Prognosis; Treatment


Acute heart failure (AHF) is one of the burdensome diseases affecting a considerable proportion of the population. Recently, it has been demonstrated that micro-ribonucleic acids (miRNAs) can exert diagnostic, prognostic, and therapeutic roles in a variety of conditions including AHF. These molecules play essential roles in HF-related pathophysiology, particularly, cardiac fibrosis, and hypertrophy. Some miRNAs namely miRNA-423-5p are reported to have both diagnostic and prognostic capabilities. However, some studies suggest that combination of biomarkers is a much better way to achieve the highest accuracy such as the combination of miRNAs and N-terminal pro b-type Natriuretic Peptide (NT pro-BNP). Therefore, this review discusses different views towards various roles of miRNAs in AHF. [GMJ.2020;9:e1818]


Zipes DP, Libby P, Bonow RO, Mann DL, Tomaselli GF. Braunwald's Heart Disease A Textbook of Cardiovascular Medicine. Elsevier Health Sciences; 2018.

Yancy CW, Jessup M, Bozkurt B. for the Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association. J Am Coll Cardiol. 2013;62:1495-539.

von Lueder TG, Agewall S. The burden of heart failure in the general population: a clearer and more concerning picture. J Thorac Dis. 2018;10(Suppl 17):S1934.

PMid:30023084 PMCid:PMC6036024

Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Heart Fail Rev. 2017;3(1):7-11.

Daniels SR. Acute vs. chronic heart failure. J Pediatr. 2006;149(1):A3.

Richards M, Di Somma S, Mueller C, Nowak R, Peacock WF, Ponikowski P et al. Atrial fibrillation impairs the diagnostic performance of cardiac natriuretic peptides in dyspneic patients: results from the BACH Study (Biomarkers in ACute Heart Failure). JACC: Heart Failure. 2013;1(3):192-9.


Christenson RH, Azzazy HME, Duh S-H, Maynard S, Seliger SL, Defilippi CR. Impact of increased body mass index on accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP for diagnosis of decompensated heart failure and prediction of all-cause mortality. Clin Chem. 2010;56(4):633-41.


Felker GM, Ahmad T, Anstrom KJ, Adams KF, Cooper LS, Ezekowitz JA et al. Rationale and design of the GUIDE-IT study: guiding evidence based therapy using biomarker intensified treatment in heart failure. JACC: Heart Failure. 2014;2(5):457-65.

PMid:25194287 PMCid:PMC4194159

Tao J, Li SF, Xu M. [The roles of microRNA in the diagnosis and therapy for cardiovascular diseases]. [Progress in physiology]. 2011;42(5):335-9.

Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15(1):38.

PMid:25960691 PMCid:PMC4424445

Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016;44(8):3865-77.

PMid:26921406 PMCid:PMC4856985

Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee S-S. Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Molecular Therapy-Nucleic Acids. 2017;8:132-43.

PMid:28918016 PMCid:PMC5496203

Jeon T-I, Osborne TF. miRNA and cholesterol homeostasis. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2016;1861(12):2041-6.

PMid:26778752 PMCid:PMC4980302

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843-54.

Kwon C, Han Z, Olson EN, Srivastava D. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A. 2005;102(52):18986-91.

PMid:16357195 PMCid:PMC1315275

Ali Sheikh MS, Salma U, Zhang B, Chen J, Zhuang J, Ping Z. Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress. Oxid Med Cell Longev. 2016;2016:5893064-.

PMid:27379177 PMCid:PMC4917723

Romaine SPR, Tomaszewski M, Condorelli G, Samani NJ. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart. 2015;101(12):921-8.

PMid:25814653 PMCid:PMC4484262

Condorelli G, Latronico MVG, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol. 2014;63(21):2177-87.


Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733-41.

PMid:20847327 PMCid:PMC4846276

Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids-the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8(8):467.

PMid:21647195 PMCid:PMC3423224

Van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A. 2006;103(48):18255-60.

PMid:17108080 PMCid:PMC1838739

Sayed D, Hong C, Chen I-Y, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007;100(3):416-24.


Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo MA et al. Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation. 2009;120(23):2377-85.

PMid:19933931 PMCid:PMC2825656

Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13(5):613.


Pan Z, Sun X, Ren J, Li X, Gao X, Lu C et al. miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS One. 2012;7(11):e50515.

PMid:23226300 PMCid:PMC3511560

Lozano-Velasco E, Galiano-Torres J, Jodar-Garcia A, Aranega AE, Franco D. miR-27 and miR-125 distinctly regulate muscle-enriched transcription factors in cardiac and skeletal myocytes. BioMed research international. 2015;2015.

PMid:26221592 PMCid:PMC4499371

Li H, Li S, Yu B, Liu S. Expression of miR-133 and miR-30 in chronic atrial fibrillation in canines. Mol Med Report. 2012;5(6):1457-60.


Thum T. Noncoding RNAs and myocardial fibrosis. Nature Reviews Cardiology. 2014;11(11):655.


Zhang Y, Sun L, Zhang Y, Liang H, Li X, Cai R et al. Overexpression of microRNA-1 causes atrioventricular block in rodents. Int J Biol Sci. 2013;9(5):455.

PMid:23678295 PMCid:PMC3654494

Silva DCPd, Carneiro FD, Almeida KCd, Fernandes-Santos C. Role of miRNAs on the Pathophysiology of Cardiovascular Diseases. Arq Bras Cardiol. 2018;111(5):738-46.

Lee S-Y, Lee CY, Ham O, Moon JY, Lee J, Seo H-H et al. microRNA-133a attenuates cardiomyocyte hypertrophy by targeting PKCδ and Gq. Mol Cell Biochem. 2018;439(1-2):105-15.


Wu Y, Wang YQ, Wang BX. MicroRNA-133a attenuates isoproterenol-induced neonatal rat cardiomyocyte hypertrophy by downregulating L-type calcium channel α1C subunit gene expression. Arq Bras Cardiol. 2013;41(6):507-13.

Stelzer JE, Brickson SL, Locher MR, Moss RL. Role of myosin heavy chain composition in the stretch activation response of rat myocardium. J Physiol Pharmacol. 2007;579(1):161-73.

PMid:17138609 PMCid:PMC2075383

Callis TE, Pandya K, Seok HY, Tang R-H, Tatsuguchi M, Huang Z-P et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest. 2009;119(9):2772-86.

PMid:19726871 PMCid:PMC2735902

Tony H, Meng K, Wu B, Yu A, Zeng Q, Yu K et al. MicroRNA-208a dysregulates apoptosis genes expression and promotes cardiomyocyte apoptosis during ischemia and its silencing improves cardiac function after myocardial infarction. Mediators Inflamm. 2015;2015.

PMid:26688617 PMCid:PMC4673358

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980.


Da Costa Martins PA, De Windt LJ. MicroRNAs in control of cardiac hypertrophy. Cardiovasc Res. 2012;93(4):563-72.


Sayed D, He M, Hong C, Gao S, Rane S, Yang Z et al. MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J Biol Chem. 2010;285(26):20281-90.

PMid:20404348 PMCid:PMC2888441

Wong LL, Wang J, Liew OW, Richards AM, Chen YT. MicroRNA and Heart Failure. Int J Mol Sci. 2016;17(4):502.

PMid:27058529 PMCid:PMC4848958

Wang Y-S, Zhou J, Hong K, Cheng X-S, Li Y-G. MicroRNA-223 displays a protective role against cardiomyocyte hypertrophy by targeting cardiac troponin I-interacting kinase. Cell Physiol Biochem. 2015;35(4):1546-56.


Bao Q, Chen L, Li J, Zhao M, Wu S, Wu W et al. Role of microRNA-124 in cardiomyocyte hypertrophy inducedby angiotensin II. Cell Mol Biol. 2017;63(4):23-7.


Shieh JTC, Huang Y, Gilmore J, Srivastava D. Elevated miR-499 levels blunt the cardiac stress response. PLoS One. 2011;6(5):e19481.

PMid:21573063 PMCid:PMC3090396

Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104(2):170-8.


Cheng R, Dang R, Zhou Y, Ding M, Hua H. MicroRNA-98 inhibits TGF-β1-induced differentiation and collagen production of cardiac fibroblasts by targeting TGFBR1. Hum Cell. 2017;30(3):192-200.


Wang J, Huang W, Xu R, Nie Y, Cao X, Meng J et al. Micro RNA‐24 regulates cardiac fibrosis after myocardial infarction. J Cell Mol Med. 2012;16(9):2150-60.

PMid:22260784 PMCid:PMC3822985

Lai K-B, Sanderson JE, Izzat MB, Yu C-M. Micro-RNA and mRNA myocardial tissue expression in biopsy specimen from patients with heart failure. Int J Cardiol. 2015;199:79-83.


He Q, Wang CM, Qin JY, Zhang YJ, Xia DS, Chen X et al. Effect of miR-203 expression on myocardial fibrosis. Eur Rev Med Pharmacol Sci. 2017;21(4):837-42.

Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2(1):89.

PMid:19454029 PMCid:PMC2694820

Patnaik SK, Mallick R, Yendamuri S. Detection of microRNAs in dried serum blots. Anal Biochem. 2010;407(1):147-9.

PMid:20696125 PMCid:PMC2947447

Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010;3(6):499-506.


Schmitter D, Cotter G, Voors AA. Clinical use of novel biomarkers in heart failure: towards personalized medicine. Heart Fail Rev. 2014;19(3):369-81.


Vogel B, Keller A, Frese KS, Leidinger P, Sedaghat-Hamedani F, Kayvanpour E et al. Multivariate miRNA signatures as biomarkers for non-ischaemic systolic heart failure. Eur Heart J. 2013;34(36):2812-23.


Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. 2012;14(2):147-54.


Dickinson BA, Semus HM, Montgomery RL, Stack C, Latimer PA, Lewton SM et al. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension‐induced heart failure. Eur J Heart Fail. 2013;15(6):650-9.


Yan H, Ma F, Zhang Y, Wang C, Qiu D, Zhou K et al. miRNAs as biomarkers for diagnosis of heart failure: A systematic review and meta-analysis. Medicine. 2017;96(22):e6825-e.

PMid:28562533 PMCid:PMC5459698

Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106(6):1035.


Fan K-L, Zhang H-F, Shen J, Zhang Q, Li X-L. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J. 2013;65(1):12-6.

PMid:23438607 PMCid:PMC3860780

Goretti E, Seronde MF, Vausort M, Gayat E, Thum T, Cohen-Solal A et al. Circulating microRNAs and outcome in patients with acute heart failure. Cardiovasc Res. 2014;103.

Tutarel O, Dangwal S, Bretthauer J, Westhoff-Bleck M, Roentgen P, Anker SD et al. Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol. 2013;167(1):63-6.


Vegter EL, Schmitter D, Hagemeijer Y, Ovchinnikova ES, van der Harst P, Teerlink JR et al. Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure. Int J Cardiol. 2016;224:231-9.


Ellis KL, Cameron VA, Troughton RW, Frampton CM, Ellmers LJ, Richards AM. Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients. Eur J Heart Fail. 2013;15(10):1138-47.


Chen W, Li S. Circulating microRNA as a novel biomarker for pulmonary arterial hypertension due to congenital heart disease. Pediatr Cardiol. 2017;38(1):86-94.


Watson CJ, Gupta SK, O'Connell E, Thum S, Glezeva N, Fendrich J et al. MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure. Eur J Heart Fail. 2015;17(4):405-15.

PMid:25739750 PMCid:PMC4418397

Olivieri F, Antonicelli R, Lorenzi M, D'Alessandra Y, Lazzarini R, Santini G et al. Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol. 2013;167(2):531-6.


Li G, Song Y, Li YD, Jie LJ, Wu WY, Li JZ et al. Circulating miRNA-302 family members as potential biomarkers for the diagnosis of acute heart failure. Biomark Med. 2018;12(8):871-80.


Ovchinnikova ES, Schmitter D, Vegter EL, ter Maaten JM, Valente MAE, Liu LCY et al. Signature of circulating microRNAs in patients with acute heart failure. Eur J Heart Fail. 2016;18(4):414-23.


Wu T, Chen Y, Du Y, Tao J, Zhou Z, Yang Z. Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy. Cell Physiol Biochem. 2018;46(5):1939-50.


Seronde M-F, Vausort M, Gayat E, Goretti E, Ng LL, Squire IB et al. Circulating microRNAs and outcome in patients with acute heart failure. PLoS One. 2015;10(11):e0142237.

PMid:26580972 PMCid:PMC4651494

Wong LL, Zou R, Zhou L, Lim JY, Phua DCY, Liu C et al. Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes. J Am Coll Cardiol. 2019;73(11):1300-13.


Oliveira-Carvalho V, Da Silva MMF, Guimaraes GV, Bacal F, Bocchi EA. MicroRNAs: new players in heart failure. Molecular biology reports. 2013;40(3):2663-70.


Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD et al. Altered microRNA expression in human heart disease. Physiol Genomics. 2007;31(3):367-73.


Sucharov C, Bristow MR, Port JD. miRNA expression in the failing human heart: Functional correlates. J Mol Cell Cardiol. 2008;45(2):185-92.

PMid:18582896 PMCid:PMC2561965

Danowski N, Manthey I, Jakob HG, Siffert W, Peters J, Frey UH. Decreased Expression of miR-133a but Not of miR-1 is Associated with Signs of Heart Failure in Patients Undergoing Coronary Bypass Surgery. Cardiology. 2013;125(2):125-30.


Weckbach LT, Grabmaier U, Clauss S, Wakili R. MicroRNAs as a diagnostic tool for heart failure and atrial fibrillation. Curr Opin Pharmacol. 2016;27:24-30.


Pourafkari L, Tajlil A, Nader ND. Biomarkers in diagnosing and treatment of acute heart failure. Biomark Med. 2019;13(14):1235-49.


Schneider S, Silvello D, Martinelli NC, Garbin A, Biolo A, Clausell N et al. Plasma levels of microRNA-21, -126 and -423-5p alter during clinical improvement and are associated with the prognosis of acute heart failure. Mol Med Rep. 2018;17(3):4736-46.


Xiao J, Gao R, Bei Y, Zhou Q, Zhou Y, Zhang H et al. Circulating miR-30d predicts survival in patients with acute heart failure. Cell Physiol Biochem. 2017;41(3):865-74.

PMid:28214846 PMCid:PMC5509048

Bruno N, ter Maaten JM, Ovchinnikova ES, Vegter EL, Valente MAE, van der Meer P et al. MicroRNAs relate to early worsening of renal function in patients with acute heart failure. Int J Cardiol. 2016;203:564-9.


Wang Z. The guideline of the design and validation of MiRNA mimics. MicroRNA and Cancer. Springer; 2011. p. 211-23.


Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005;438(7068):685.


Hullinger TG, Montgomery RL, Seto AG, Dickinson BA, Semus HM, Lynch JM et al. Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res. 2012;110(1):71-81.

PMid:22052914 PMCid:PMC3354618

Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124(14):1537-47.

PMid:21900086 PMCid:PMC3353551

Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskamper J et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation. 2009;119(9):1241-52.

PMid:19237664 PMCid:PMC4298485

Zhang Y, Huang X-R, Wei L-H, Chung ACK, Yu C-M, Lan H-Y. miR-29b as a Therapeutic Agent for Angiotensin II-induced Cardiac Fibrosis by Targeting TGF-β/Smad3 signaling. Mol Ther. 2014;22(5):974-85.

PMid:24569834 PMCid:PMC4015231

Kumarswamy R, Lyon AR, Volkmann I, Mills AM, Bretthauer J, Pahuja A et al. SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway. Eur Heart J. 2012;33(9):1067-75.

PMid:22362515 PMCid:PMC3341631

Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S et al. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat Commun. 2012;3:1078.

PMid:23011132 PMCid:PMC3657998

Fiedler J, Jazbutyte V, Kirchmaier BC, Gupta SK, Lorenzen J, Hartmann D et al. MicroRNA-24 regulates vascularity after myocardial infarction. Circulation. 2011;124(6):720-30.


Pan LJ, Wang X, Ling Y, Gong H. MiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via targeting BIM. Eur Rev Med Pharmacol Sci. 2017;21(13):3088-97.

Xiao X, Lu Z, Lin V, May A, Shaw DH, Wang Z et al. MicroRNA miR-24-3p Reduces Apoptosis and Regulates Keap1-Nrf2 Pathway in Mouse Cardiomyocytes Responding to Ischemia/Reperfusion Injury. Oxid Med Cell Longev. 2018;2018:7042105.

PMid:30622671 PMCid:PMC6304907

Meloni M, Marchetti M, Garner K, Littlejohns B, Sala-Newby G, Xenophontos N et al. Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. Mol Ther. 2013;21(7):1390-402.

PMid:23774796 PMCid:PMC3702112

Xu M, Wu HD, Li RC, Zhang HB, Wang M, Tao J et al. Mir-24 regulates junctophilin-2 expression in cardiomyocytes. Circ Res. 2012;111(7):837-41.

PMid:22891046 PMCid:PMC3611051

Liu F, Yin L, Zhang L, Liu W, Liu J, Wang Y et al. Trimetazidine improves right ventricular function by increasing miR-21 expression. Int J Mol Med. 2012;30(4):849-55.


Chini VP. Micro-RNAs and next generation sequencing: new perspectives in heart failure. Clin Chim Acta. 2015;443:114-9.


Biyashev D, Veliceasa D, Topczewski J, Topczewska JM, Mizgirev I, Vinokour E et al. miR-27b controls venous specification and tip cell fate. Blood. 2012;119(11):2679-87.

PMid:22207734 PMCid:PMC3311282

Pan W, Zhong Y, Cheng C, Liu B, Wang L, Li A et al. MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy. PLoS One. 2013;8(1):e53950.

PMid:23326547 PMCid:PMC3541228

Kim GH, Samant SA, Earley JU, Svensson EC. Translational control of FOG-2 expression in cardiomyocytes by microRNA-130a. PLoS One. 2009;4(7):e6161.

PMid:19582148 PMCid:PMC2701631

Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW et al. MicroRNAs in the human heart. Circulation. 2007;116(3):258-67.


Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskämper J et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation. 2009;119(9):1241-52.

PMid:19237664 PMCid:PMC4298485

Duan Q, Chen C, Yang L, Li N, Gong W, Li S et al. MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo. J Transl Med. 2015;13(1):363.

PMid:26572862 PMCid:PMC4647486

Chinchilla A, Lozano E, Daimi H, Esteban FJ, Crist C, Aranega AE et al. MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression. Cardiovasc Res. 2010;89(1):98-108.


Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 2010;107(30):13450-5.

PMid:20624982 PMCid:PMC2922125

Zhu N, Zhang D, Chen S, Liu X, Lin L, Huang X et al. Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration. Atherosclerosis. 2011;215(2):286-93.


Weber M, Baker MB, Moore JP, Searles CD. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun. 2010;393(4):643-8.

PMid:20153722 PMCid:PMC3717387

Zhang X, Wang X, Zhu H, Zhu C, Wang Y, Pu WT et al. Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death. J Mol Cell Cardiol. 2010;49(5):841-50.

PMid:20708014 PMCid:PMC2949485

Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261-71.

PMid:18694565 PMCid:PMC2685763

Li D, Yang P, Xiong Q, Song X, Yang X, Liu L et al. MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. J Hypertens. 2010;28(8):1646-54.


Fish JE, Santoro MM, Morton SU, Yu S, Yeh R-F, Wythe JD et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272-84.

PMid:18694566 PMCid:PMC2604134

Matkovich SJ, Van Booven DJ, Youker KA, Torre-Amione G, Diwan A, Eschenbacher WH et al. Reciprocal regulation of myocardial miR and mRNA in human cardiomyopathy and reversal of the miR signature by biomechanical support. Circulation. 2009;119(9):1263.

PMid:19237659 PMCid:PMC2749457

Han M, Toli J, Abdellatif M. MicroRNAs in the cardiovascular system. Current opinion in cardiology. 2011;26(3):181-9.


Zhu H, Yang Y, Wang Y, Li J, Schiller PW, Peng T. MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by down-regulating Sirt1. Cardiovasc Res. 2011;92(1):75-84.


Zhao T, Li J, Chen AF. MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1. American Journal of Physiology-Endocrinology and Metabolism. 2010;299(1):E110-E6.

PMid:20424141 PMCid:PMC2904051

Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui Y et al. Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro-RNA-132. Circ Res. 2011;109(8):894-906.

PMid:21868695 PMCid:PMC3623091

Wang J, Jia Z, Zhang C, Sun M, Wang W, Chen P et al. miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects on Pdcd4 and Pacs2. RNA Biol. 2014;11(4):339-50.

PMid:24646523 PMCid:PMC4075519

Zhang B, Zhou M, Li C, Zhou J, Li H, Zhu D et al. MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7. PLoS One. 2014;9(6):e100298.

PMid:24941323 PMCid:PMC4062536

Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C et al. Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood. 2010;115(23):4944-50.


Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324(5935):1710-3.


Santulli G. MicroRNAs and endothelial (Dys) function. J Cell Physiol. 2016;231(8):1638-44.

PMid:26627535 PMCid:PMC4871250

Smits M, Mir SE, Nilsson RJA, van der Stoop PM, Niers JM, Marquez VE et al. Down-regulation of miR-101 in endothelial cells promotes blood vessel formation through reduced repression of EZH2. PLoS One. 2011;6(1):e16282.

PMid:21297974 PMCid:PMC3030563

Yuan Y, Zhang Z, Wang Z, Liu J. MiRNA-27b Regulates Angiogenesis by Targeting AMPK in Mouse Ischemic Stroke Model. Neuroscience. 2019;398:12-22.


Ren X-P, Wu J, Wang X, Sartor MA, Jones K, Qian J et al. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation. 2009;119(17):2357-66.

PMid:19380620 PMCid:PMC2746735

Huang ZQ, Xu W, Wu JL, Lu X, Chen XM. MicroRNA-374a protects against myocardial ischemia-reperfusion injury in mice by targeting the MAPK6 pathway. Life Sci. 2019;232:116619.


Chen Z, Qi Y, Gao C. Cardiac myocyte-protective effect of microRNA-22 during ischemia and reperfusion through disrupting the caveolin-3/eNOS signaling. Int J Clin Exp Pathol. 2015;8(5):4614-26.

Saif J, Emanueli C. miRNAs in post-ischaemic angiogenesis and vascular remodelling. Biochem Soc Trans. 2014;42(6):1629-36.


Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460(7256):705.

PMid:19578358 PMCid:PMC2769203

Zhou Y, Deng L, Zhao D, Chen L, Yao Z, Guo X et al. Micro RNA-503 promotes angiotensin II-induced cardiac fibrosis by targeting Apelin-13. J Cell Mol Med. 2016;20(3):495-505.

PMid:26756969 PMCid:PMC4759464

Tao L, Bei Y, Chen P, Lei Z, Fu S, Zhang H et al. Crucial role of miR-433 in regulating cardiac fibrosis. Theranostics. 2016;6(12):2068.

PMid:27698941 PMCid:PMC5039681

Yuan J, Chen H, Ge D, Xu Y, Xu H, Yang Y et al. Mir-21 promotes cardiac fibrosis after myocardial infarction via targeting Smad7. Cell Physiol Biochem. 2017;42(6):2207-19.


Creemers EE, van Rooij E. Function and therapeutic potential of noncoding RNAs in cardiac fibrosis. Circ Res. 2016;118(1):108-18.


Shan H, Zhang Y, Cai B, Chen X, Fan Y, Yang L et al. Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling. Int J Cardiol. 2013;167(6):2798-805.


Osbourne A, Calway T, Broman M, McSharry S, Earley J, Kim GH. Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias. J Mol Cell Cardiol. 2014;74:53-63.

PMid:24819345 PMCid:PMC4412372

Prasad SVN, Gupta MK, Duan Z-H, Surampudi VSK, Liu C-G, Kotwal A et al. A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. PLoS One. 2017;12(3):e0170456.

PMid:28329018 PMCid:PMC5362047

Kontaraki JE, Marketou ME, Zacharis EA, Parthenakis FI, Vardas PE. MiR-1, miR-9 and miR-126 levels in peripheral blood mononuclear cells of patients with essential hypertension associate with prognostic indices of ambulatory blood pressure monitoring. Eur Heart J. 2013;34(suppl_1).

Vegter EL, Ovchinnikova ES, van Veldhuisen DJ, Jaarsma T, Berezikov E, van der Meer P et al. Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations. Clin Res Cardiol. 2017;106(8):598-609.

PMid:28293796 PMCid:PMC5529487

Kontaraki JE, Marketou ME, Zacharis EA, Parthenakis FI, Vardas PE. Mir-143/mir-145 levels in peripheral blood mononuclear cells associate with ambulatory blood pressure monitoring parameters in patients with essential hypertension. Eur Heart J. 2013;34(suppl_1).

Li X, Liu CY, Li YS, Xu J, Li DG, Li X et al. Deep RNA sequencing elucidates microRNA-regulated molecular pathways in ischemic cardiomyopathy and nonischemic cardiomyopathy. Genet Mol Res. 2016;15(2).

Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010;107(5):677-84.


Cakmak HA, Coskunpinar E, Ikitimur B, Barman HA, Karadag B, Tiryakioglu NO et al. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med. 2015;16(6):431-7.


Zhang J, Xing Q, Zhou X, Li J, Li Y, Zhang L et al. Circulating miRNA‑21 is a promising biomarker for heart failure. Mol Med Report. 2017;16(5):7766-74.


Deng X, Liu Y, Luo M, Wu J, Ma R, Wan Q et al. Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus. Oncotarget. 2017;8(38):63038.

PMid:28968969 PMCid:PMC5609901

Marfella R, Di Filippo C, Potenza N, Sardu C, Rizzo MR, Siniscalchi M et al. Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders. Eur J Heart Fail. 2013;15(11):1277-88.


Dawson K, Wakili R, Ördög B, Clauss S, Chen Y, Iwasaki Y et al. MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation. Circulation. 2013;127(14):1466-75.


Zhao DS, Chen Y, Jiang H, Lu JP, Zhang G, Geng J et al. Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure. Cardiovasc Pathol. 2013;22(6):444-50.


Greco S, Fasanaro P, Castelvecchio S, D'Alessandra Y, Arcelli D, Di Donato M et al. MicroRNA dysregulation in diabetic ischemic heart failure patients. Diabetes. 2012;61(6):1633-41.

PMid:22427379 PMCid:PMC3357263

Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M et al. Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res. 2013;113(3):322-6.


Enes Coşkun M, Kervancıoğlu M, Öztuzcu S, Yılmaz Coşkun F, Ergün S, Başpınar O et al. Plasma microRNA profiling of children with idiopathic dilated cardiomyopathy. Biomarkers. 2016;21(1):56-61.


Mukai N, Nakayama Y, Murakami S, Tanahashi T, Sessler DI, Ishii S et al. Potential contribution of erythrocyte microRNA to secondary erythrocytosis and thrombocytopenia in congenital heart disease. Pediatr Res. 2018;83(4):866.


Wong LL, Armugam A, Sepramaniam S, Karolina DS, Lim KY, Lim JY et al. Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail. 2015;17(4):393-404.


Fichtlscherer S, Zeiher AM, Dimmeler S. Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol. 2011;31(11):2383-90.


Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J. 2011;75(2):336-40.


Wei XJ, Han M, Yang FY, Wei GC, Liang ZG, Yao H et al. Biological significance of miR-126 expression in atrial fibrillation and heart failure. Braz J Med Biol Res. 2015;48(11):983-9.

PMid:26313139 PMCid:PMC4671524

Nandi SS, Duryee MJ, Shahshahan HR, Thiele GM, Anderson DR, Mishra PK. Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading. Am J Transl Res. 2015;7(4):683.

Nair N, Kumar S, Gongora E, Gupta S. Circulating miRNA as novel markers for diastolic dysfunction. Mol Cell Biochem. 2013;376(1-2):33-40.


Miyamoto SD, Karimpour-Fard A, Peterson V, Auerbach SR, Stenmark KR, Stauffer BL et al. Circulating microRNA as a biomarker for recovery in pediatric dilated cardiomyopathy. J Heart Lung Transplant. 2015;34(5):724-33.


Zeng X, Li X, H W. Expression of circulating microRNA-182, CITED2 and HIF-1 in ischemic cardiomyopathy and their correlation. J Clin Cardiol. 2017;33:119-22.

Akat KM, Moore-McGriff DV, Morozov P, Brown M, Gogakos T, Da Rosa JC et al. Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. Proc Natl Acad Sci U S A. 2014;111(30):11151-6.

PMid:25012294 PMCid:PMC4121804

Leger KJ, Singh S, Canseco D, vonGrote EC, Karim-Ud-Din S, Collins SC et al. Identification of Novel Circulating microRNAs in Ischemic Cardiomyopathy Utilizing Whole Blood microRNA Profiling. Am Heart Assoc; 2013.

van Boven N, Kardys I, van Vark LC, Akkerhuis KM, de Ronde MWJ, Khan MAF et al. Serially measured circulating microRNAs and adverse clinical outcomes in patients with acute heart failure. Eur J Heart Fail. 2018;20(1):89-96.


How to Cite
Sadat-Ebrahimi, S.-R., & Aslanabadi, N. (2020). Role of MicroRNAs in Diagnosis, Prognosis, and Treatment of Acute Heart Failure: Ambassadors from Intracellular Zone. Galen Medical Journal, 9, e1818.
Review Article