Small engine, big power: microRNAs as regulators of cardiac diseases and regeneration

Darukeshwara Joladarashi, Rajarajan Amirthalingam Thandavarayan, Sahana Suresh Babu, Prasanna Krishnamurthy, Darukeshwara Joladarashi, Rajarajan Amirthalingam Thandavarayan, Sahana Suresh Babu, Prasanna Krishnamurthy

Abstract

Cardiac diseases are the predominant cause of human mortality in the United States and around the world. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to modulate a wide range of biological functions under various pathophysiological conditions. miRNAs alter target expression by post-transcriptional regulation of gene expression. Numerous studies have implicated specific miRNAs in cardiovascular development, pathology, regeneration and repair. These observations suggest that miRNAs are potential therapeutic targets to prevent or treat cardiovascular diseases. This review focuses on the emerging role of miRNAs in cardiac development, pathogenesis of cardiovascular diseases, cardiac regeneration and stem cell-mediated cardiac repair. We also discuss the novel diagnostic and therapeutic potential of these miRNAs and their targets in patients with cardiac diseases.

Figures

Figure 1
Figure 1
Role of miRNAs in cardiac development, disease and regeneration. Increasing, Decreasing, ⟞ Inhibiting.

References

    1. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Blaha M.J., Dai S., Ford E.S., Fox C.S., Franco S., et al. Heart disease and stroke statistics—2014 update: A report from the American Heart Association. Circulation. 2014;129:e28–e292. doi: 10.1161/01.cir.0000441139.02102.80.
    1. Mathers C.D., Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3:e442. doi: 10.1371/journal.pmed.0030442.
    1. Lopez A.D., Mathers C.D., Ezzati M., Jamison D.T., Murray C.J. Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet. 2006;367:1747–1757. doi: 10.1016/S0140-6736(06)68770-9.
    1. Chen J., Wang D.Z. MicroRNAs in cardiovascular development. J. Mol. Cell. Cardiol. 2012;52:949–957. doi: 10.1016/j.yjmcc.2012.01.012.
    1. Liu N., Olson E.N. MicroRNA regulatory networks in cardiovascular development. Dev. Cell. 2010;18:510–525. doi: 10.1016/j.devcel.2010.03.010.
    1. Kishore R., Verma S.K., Mackie A.R., Vaughan E.E., Abramova T.V., Aiko I., Krishnamurthy P. Bone marrow progenitor cell therapy-mediated paracrine regulation of cardiac miRNA-155 modulates fibrotic response in diabetic hearts. PLoS One. 2013;8:e60161.
    1. Liu D., Fan J., Zeng W., Zhou Y., Ingvarsson S., Chen H. Quantitative analysis of miRNA expression in several developmental stages of human livers. Hepatol. Res. 2010;40:813–822. doi: 10.1111/j.1872-034X.2010.00683.x.
    1. Abdelmohsen K., Srikantan S., Kuwano Y., Gorospe M. miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc. Natl. Acad. Sci. USA. 2008;105:20297–20302. doi: 10.1073/pnas.0809376106.
    1. Bartel D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297. doi: 10.1016/S0092-8674(04)00045-5.
    1. Cascio S., D’Andrea A., Ferla R., Surmacz E., Gulotta E., Amodeo V., Bazan V., Gebbia N., Russo A. miR-20b modulates VEGF expression by targeting HIF-1α and STAT3 in MCF-7 breast cancer cells. J. Cell. Physiol. 2010;224:242–249.
    1. El Ouaamari A., Baroukh N., Martens G.A., Lebrun P., Pipeleers D., van Obberghen E. miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells. Diabetes. 2008;57:2708–2717. doi: 10.2337/db07-1614.
    1. Esau C., Davis S., Murray S.F., Yu X.X., Pandey S.K., Pear M., Watts L., Booten S.L., Graham M., McKay R., et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3:87–98. doi: 10.1016/j.cmet.2006.01.005.
    1. Fish J.E., Srivastava D. MicroRNAs: Opening a new vein in angiogenesis research. Sci. Signal. 2009;2:pe1.
    1. Ivey K.N., Muth A., Arnold J., King F.W., Yeh R.F., Fish J.E., Hsiao E.C., Schwartz R.J., Conklin B.R., Bernstein H.S., et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008;2:219–229. doi: 10.1016/j.stem.2008.01.016.
    1. Urbich C., Kuehbacher A., Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc. Res. 2008;79:581–588. doi: 10.1093/cvr/cvn156.
    1. Van Rooij E., Sutherland L.B., Thatcher J.E., DiMaio J.M., Naseem R.H., Marshall W.S., Hill J.A., Olson E.N. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc. Natl. Acad. Sci. USA. 2008;105:13027–13032. doi: 10.1073/pnas.0805038105.
    1. Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–854. doi: 10.1016/0092-8674(93)90529-Y.
    1. Wightman B., Ha I., Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855–862. doi: 10.1016/0092-8674(93)90530-4.
    1. Lewis B.P., Burge C.B., Bartel D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20. doi: 10.1016/j.cell.2004.12.035.
    1. Friedman R.C., Farh K.K., Burge C.B., Bartel D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.
    1. Lee Y., Kim M., Han J., Yeom K.H., Lee S., Baek S.H., Kim V.N. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23:4051–4060. doi: 10.1038/sj.emboj.7600385.
    1. Ha M., Kim V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014;15:509–524. doi: 10.1038/nrm3838.
    1. Bartel D.P. MicroRNAs: Target recognition and regulatory functions. Cell. 2009;136:215–233. doi: 10.1016/j.cell.2009.01.002.
    1. Kim V.N., Han J., Siomi M.C. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 2009;10:126–139. doi: 10.1038/nrm2632.
    1. Guo H., Ingolia N.T., Weissman J.S., Bartel D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–840. doi: 10.1038/nature09267.
    1. Vasudevan S., Tong Y., Steitz J.A. Switching from repression to activation: MicroRNAs can up-regulate translation. Science. 2007;318:1931–1934. doi: 10.1126/science.1149460.
    1. Chi S.W., Zang J.B., Mele A., Darnell R.B. Argonaute HITS-CLIP decodes microRNA–mRNA interaction maps. Nature. 2009;460:479–486.
    1. Corrado C., Raimondo S., Chiesi A., Ciccia F., de Leo G., Alessandro R. Exosomes as intercellular signaling organelles involved in health and disease: Basic science and clinical applications. Int. J. Mol. Sci. 2013;14:5338–5366. doi: 10.3390/ijms14035338.
    1. Vo N.K., Dalton R.P., Liu N., Olson E.N., Goodman R.H. Affinity purification of microRNA-133a with the cardiac transcription factor, Hand2. Proc. Natl. Acad. Sci. USA. 2010;107:19231–19236. doi: 10.1073/pnas.1013162107.
    1. Hendrickson D.G., Hogan D.J., McCullough H.L., Myers J.W., Herschlag D., Ferrell J.E., Brown P.O. Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol. 2009;7:e1000238. doi: 10.1371/journal.pbio.1000238.
    1. Zhao Y., Ransom J.F., Li A., Vedantham V., von Drehle M., Muth A.N., Tsuchihashi T., McManus M.T., Schwartz R.J., Srivastava D. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell. 2007;129:303–317. doi: 10.1016/j.cell.2007.03.030.
    1. Rao P.K., Toyama Y., Chiang H.R., Gupta S., Bauer M., Medvid R., Reinhardt F., Liao R., Krieger M., Jaenisch R., et al. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ. Res. 2009;105:585–594. doi: 10.1161/CIRCRESAHA.109.200451.
    1. Olson E.N., Schneider M.D. Sizing up the heart: Development redux in disease. Genes Dev. 2003;17:1937–1956. doi: 10.1101/gad.1110103.
    1. Li F., Wang X., Capasso J.M., Gerdes A.M. Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J. Mol. Cell. Cardiol. 1996;28:1737–1746. doi: 10.1006/jmcc.1996.0163.
    1. Kajstura J., Zhang X., Reiss K., Szoke E., Li P., Lagrasta C., Cheng W., Darzynkiewicz Z., Olivetti G., Anversa P. Myocyte cellular hyperplasia and myocyte cellular hypertrophy contribute to chronic ventricular remodeling in coronary artery narrowing-induced cardiomyopathy in rats. Circ. Res. 1994;74:383–400. doi: 10.1161/01.RES.74.3.383.
    1. Paradis A., Xiao D., Zhou J., Zhang L. Endothelin-1 promotes cardiomyocyte terminal differentiation in the developing heart via heightened DNA methylation. Int. J. Med. Sci. 2014;11:373–380. doi: 10.7150/ijms.7802.
    1. Schupp M.O., Waas M., Chun C.Z., Ramchandran R. Transcriptional inhibition of etv2 expression is essential for embryonic cardiac development. Dev. Biol. 2014;393:71–83. doi: 10.1016/j.ydbio.2014.06.019.
    1. Deb A., Ubil E. Cardiac fibroblast in development and wound healing. J. Mol. Cell. Cardiol. 2014;70:47–55. doi: 10.1016/j.yjmcc.2014.02.017.
    1. Ieda M. Heart development and regeneration via cellular interaction and reprogramming. Keio J. Med. 2013;62:99–106. doi: 10.2302/kjm.2012-0020-RE.
    1. Peralta M., Gonzalez-Rosa J.M., Marques I.J., Mercader N. The epicardium in the embryonic and adult zebrafish. J. Dev. Biol. 2014;2:101–116. doi: 10.3390/jdb2020101.
    1. Liu N., Williams A.H., Kim Y., McAnally J., Bezprozvannaya S., Sutherland L.B., Richardson J.A., Bassel-Duby R., Olson E.N. An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proc. Natl. Acad. Sci. USA. 2007;104:20844–20849. doi: 10.1073/pnas.0710558105.
    1. Zhao Y., Samal E., Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005;436:214–220. doi: 10.1038/nature03817.
    1. Liu N., Bezprozvannaya S., Williams A.H., Qi X., Richardson J.A., Bassel-Duby R., Olson E.N. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 2008;22:3242–3254. doi: 10.1101/gad.1738708.
    1. Ventura A., Young A.G., Winslow M.M., Lintault L., Meissner A., Erkeland S.J., Newman J., Bronson R.T., Crowley D., Stone J.R., et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132:875–886. doi: 10.1016/j.cell.2008.02.019.
    1. Thum T., Galuppo P., Wolf C., Fiedler J., Kneitz S., van Laake L.W., Doevendans P.A., Mummery C.L., Borlak J., Haverich A., et al. MicroRNAs in the human heart: A clue to fetal gene reprogramming in heart failure. Circulation. 2007;116:258–267. doi: 10.1161/CIRCULATIONAHA.107.687947.
    1. Watanabe K., Thandavarayan R.A., Harima M., Sari F.R., Gurusamy N., Veeraveedu P.T., Mito S., Arozal W., Sukumaran V., Laksmanan A.P., et al. Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. Curr. Cardiol. Rev. 2010;6:280–290. doi: 10.2174/157340310793566145.
    1. Watanabe K., Thandavarayan R.A., Gurusamy N., Zhang S., Muslin A.J., Suzuki K., Tachikawa H., Kodama M., Aizawa Y. Role of 14–3-3 protein and oxidative stress in diabetic cardiomyopathy. Acta Physiol. Hung. 2009;96:277–287. doi: 10.1556/APhysiol.96.2009.3.3.
    1. Thandavarayan R.A., Watanabe K., Ma M., Gurusamy N., Veeraveedu P.T., Konishi T., Zhang S., Muslin A.J., Kodama M., Aizawa Y. Dominant-negative p38α mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus. Am. J. Physiol. Heart Circ. Physiol. 2009;297:H911–H919. doi: 10.1152/ajpheart.00124.2009.
    1. Thandavarayan R.A., Giridharan V.V., Sari F.R., Arumugam S., Veeraveedu P.T., Pandian G.N., Palaniyandi S.S., Ma M., Suzuki K., Gurusamy N., et al. Depletion of 14–3-3 protein exacerbates cardiac oxidative stress, inflammation and remodeling process via modulation of MAPK/NF-κB signaling pathways after streptozotocin-induced diabetes mellitus. Cell. Physiol. Biochem. 2011;28:911–922. doi: 10.1159/000335805.
    1. McCarthy J.J., Esser K.A. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J. Appl. Physiol. 2007;102:306–313. doi: 10.1152/japplphysiol.00932.2006.
    1. Krishnamurthy P., Subramanian V., Singh M., Singh K. β1 integrins modulate β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. Hypertension. 2007;49:865–872. doi: 10.1161/01.HYP.0000258703.36986.13.
    1. Verma S.K., Krishnamurthy P., Barefield D., Singh N., Gupta R., Lambers E., Thal M., Mackie A., Hoxha E., Ramirez V., et al. Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-κB. Circulation. 2012;126:418–429. doi: 10.1161/CIRCULATIONAHA.112.112185.
    1. Rajabi M., Kassiotis C., Razeghi P., Taegtmeyer H. Return to the fetal gene program protects the stressed heart: A strong hypothesis. Heart Fail. Rev. 2007;12:331–343. doi: 10.1007/s10741-007-9034-1.
    1. Mooren F.C., Viereck J., Kruger K., Thum T. Circulating microRNAs as potential biomarkers of aerobic exercise capacity. Am. J. Physiol. Heart Circ. Physiol. 2014;306:H557–H563. doi: 10.1152/ajpheart.00711.2013.
    1. Martinelli N.C., Cohen C.R., Santos K.G., Castro M.A., Biolo A., Frick L., Silvello D., Lopes A., Schneider S., Andrades M.E., et al. An analysis of the global expression of microRNAs in an experimental model of physiological left ventricular hypertrophy. PLoS One. 2014;9:e93271. doi: 10.1371/journal.pone.0093271.
    1. Callis T.E., Pandya K., Seok H.Y., Tang R.H., Tatsuguchi M., Huang Z.P., Chen J.F., Deng Z., Gunn B., Shumate J., et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J. Clin. Investig. 2009;119:2772–2786. doi: 10.1172/JCI36154.
    1. Van Rooij E., Sutherland L.B., Liu N., Williams A.H., McAnally J., Gerard R.D., Richardson J.A., Olson E.N. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc. Natl. Acad. Sci. USA. 2006;103:18255–18260. doi: 10.1073/pnas.0608791103.
    1. Chen J.F., Murchison E.P., Tang R., Callis T.E., Tatsuguchi M., Deng Z., Rojas M., Hammond S.M., Schneider M.D., Selzman C.H., et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc. Natl. Acad. Sci. USA. 2008;105:2111–2116. doi: 10.1073/pnas.0710228105.
    1. Cheng Y., Ji R., Yue J., Yang J., Liu X., Chen H., Dean D.B., Zhang C. MicroRNAs are aberrantly expressed in hypertrophic heart: Do they play a role in cardiac hypertrophy? Am. J. Pathol. 2007;170:1831–1840. doi: 10.2353/ajpath.2007.061170.
    1. 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;100:416–424. doi: 10.1161/01.RES.0000257913.42552.23.
    1. Ikeda S., Kong S.W., Lu J., Bisping E., Zhang H., Allen P.D., Golub T.R., Pieske B., Pu W.T. Altered microRNA expression in human heart disease. Physiol. Genomics. 2007;31:367–373. doi: 10.1152/physiolgenomics.00144.2007.
    1. Tatsuguchi M., Seok H.Y., Callis T.E., Thomson J.M., Chen J.F., Newman M., Rojas M., Hammond S.M., Wang D.Z. Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J. Mol. Cell. Cardiol. 2007;42:1137–1141. doi: 10.1016/j.yjmcc.2007.04.004.
    1. Chen H., Untiveros G.M., McKee L.A., Perez J., Li J., Antin P.B., Konhilas J.P. Micro-RNA-195 and -451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One. 2012;7:e41574.
    1. Montgomery R.L., Hullinger T.G., Semus H.M., Dickinson B.A., Seto A.G., Lynch J.M., Stack C., Latimer P.A., Olson E.N., van Rooij E. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124:1537–1547. doi: 10.1161/CIRCULATIONAHA.111.030932.
    1. Bang C., Batkai S., Dangwal S., Gupta S.K., Foinquinos A., Holzmann A., Just A., Remke J., Zimmer K., Zeug A., et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J. Clin. Investig. 2014;124:2136–2146. doi: 10.1172/JCI70577.
    1. Rossi M.A. Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J. Hypertens. 1998;16:1031–1041. doi: 10.1097/00004872-199816070-00018.
    1. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol. Rev. 1999;79:215–262.
    1. Manabe I., Shindo T., Nagai R. Gene expression in fibroblasts and fibrosis: Involvement in cardiac hypertrophy. Circ. Res. 2002;91:1103–1113. doi: 10.1161/01.RES.0000046452.67724.B8.
    1. Brown R.D., Ambler S.K., Mitchell M.D., Long C.S. The cardiac fibroblast: Therapeutic target in myocardial remodeling and failure. Annu. Rev. Pharmacol. Toxicol. 2005;45:657–687. doi: 10.1146/annurev.pharmtox.45.120403.095802.
    1. Khan R., Sheppard R. Fibrosis in heart disease: Understanding the role of transforming growth factor-β in cardiomyopathy, valvular disease and arrhythmia. Immunology. 2006;118:10–24. doi: 10.1111/j.1365-2567.2006.02336.x.
    1. Martos R., Baugh J., Ledwidge M., O’Loughlin C., Conlon C., Patle A., Donnelly S.C., McDonald K. Diastolic heart failure: Evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation. 2007;115:888–895. doi: 10.1161/CIRCULATIONAHA.106.638569.
    1. Benjamin I.J., Jalil J.E., Tan L.B., Cho K., Weber K.T., Clark W.A. Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis. Circ. Res. 1989;65:657–670. doi: 10.1161/01.RES.65.3.657.
    1. Buja L.M., Willerson J.T. The role of coronary artery lesions in ischemic heart disease: Insights from recent clinicopathologic, coronary arteriographic, and experimental studies. Hum. Pathol. 1987;18:451–461. doi: 10.1016/S0046-8177(87)80030-8.
    1. Krishnamurthy P., Peterson J.T., Subramanian V., Singh M., Singh K. Inhibition of matrix metalloproteinases improves left ventricular function in mice lacking osteopontin after myocardial infarction. Mol. Cell. Biochem. 2009;322:53–62. doi: 10.1007/s11010-008-9939-6.
    1. Yang B., Lin H., Xiao J., Lu Y., Luo X., Li B., Zhang Y., Xu C., Bai Y., Wang H., et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat. Med. 2007;13:486–491. doi: 10.1038/nm1569.
    1. Ichimura A., Ruike Y., Terasawa K., Tsujimoto G. miRNAs and regulation of cell signaling. FEBS J. 2011;278:1610–1618. doi: 10.1111/j.1742-4658.2011.08087.x.
    1. Thum T., Gross C., Fiedler J., Fischer T., Kissler S., Bussen M., Galuppo P., Just S., Rottbauer W., Frantz S., et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–984. doi: 10.1038/nature07511.
    1. Roy S., Khanna S., Hussain S.R., Biswas S., Azad A., Rink C., Gnyawali S., Shilo S., Nuovo G.J., Sen C.K. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc. Res. 2009;82:21–29. doi: 10.1093/cvr/cvp015.
    1. Duisters R.F., Tijsen A.J., Schroen B., Leenders J.J., Lentink V., van der Made I., Herias V., van Leeuwen R.E., Schellings M.W., Barenbrug P., 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;104:170–178. doi: 10.1161/CIRCRESAHA.108.182535.
    1. He B., Xiao J., Ren A.J., Zhang Y.F., Zhang H., Chen M., Xie B., Gao X.G., Wang Y.W. Role of miR-1 and miR-133a in myocardial ischemic postconditioning. J. Biomed. Sci. 2011;18:22. doi: 10.1186/1423-0127-18-22.
    1. Danowski N., Manthey I., Jakob H.G., Siffert W., Peters J., Frey U.H. 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;125:125–130. doi: 10.1159/000348563.
    1. Osbourne A., Calway T., Broman M., McSharry S., Earley J., Kim G.H. Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias. J. Mol. Cell. Cardiol. 2014;74:53–63. doi: 10.1016/j.yjmcc.2014.04.024.
    1. Ucar A., Gupta S.K., Fiedler J., Erikci E., Kardasinski M., Batkai S., Dangwal S., Kumarswamy R., Bang C., Holzmann A., et al. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat. Commun. 2012;3:1078. doi: 10.1038/ncomms2090.
    1. Xiao J., Liang D., Zhang Y., Liu Y., Zhang H., Liu Y., Li L., Liang X., Sun Y., Chen Y.H. MicroRNA expression signature in atrial fibrillation with mitral stenosis. Physiol. Genomics. 2011;43:655–664. doi: 10.1152/physiolgenomics.00139.2010.
    1. Chinchilla A., Daimi H., Lozano-Velasco E., Dominguez J.N., Caballero R., Delpon E., Tamargo J., Cinca J., Hove-Madsen L., Aranega A.E., et al. PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circ. Cardiovasc. Genet. 2011;4:269–279. doi: 10.1161/CIRCGENETICS.110.958116.
    1. Wang J., Klysik E., Sood S., Johnson R.L., Wehrens X.H., Martin J.F. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc. Natl. Acad. Sci. USA. 2010;107:9753–9758. doi: 10.1073/pnas.0912585107.
    1. Wang J., Bai Y., Li N., Ye W., Zhang M., Greene S.B., Tao Y., Chen Y., Wehrens X.H., Martin J.F. Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation. Proc. Natl. Acad. Sci. USA. 2014;111:9181–9186. doi: 10.1073/pnas.1405411111.
    1. Goren Y., Meiri E., Hogan C., Mitchell H., Lebanony D., Salman N., Schliamser J.E., Amir O. Relation of reduced expression of miR-150 in platelets to atrial fibrillation in patients with chronic systolic heart failure. Am. J. Cardiol. 2014;113:976–981. doi: 10.1016/j.amjcard.2013.11.060.
    1. Xiao J., Luo X., Lin H., Zhang Y., Lu Y., Wang N., Zhang Y., Yang B., Wang Z. MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J. Biol. Chem. 2007;282:12363–12367. doi: 10.1074/jbc.C700015200.
    1. Bauters C., Lamblin N., Mc Fadden E.P., van Belle E., Millaire A., de Groote P. Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc. Diabetol. 2003;2:1. doi: 10.1186/1475-2840-2-1.
    1. Li Y., Yang C.M., Xi Y., Wu G., Shelat H., Gao S., Cheng J., Geng Y.J. MicroRNA-1/133 targeted dysfunction of potassium channels KCNE1 and KCNQ1 in human cardiac progenitor cells with simulated hyperglycemia. Int. J. Cardiol. 2013;167:1076–1078. doi: 10.1016/j.ijcard.2012.10.060.
    1. Fasanaro P., D’Alessandra Y., di Stefano V., Melchionna R., Romani S., Pompilio G., Capogrossi M.C., Martelli F. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 2008;283:15878–15883. doi: 10.1074/jbc.M800731200.
    1. Icli B., Wara A.K., Moslehi J., Sun X., Plovie E., Cahill M., Marchini J.F., Schissler A., Padera R.F., Shi J., et al. MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ. Res. 2013;113:1231–1241. doi: 10.1161/CIRCRESAHA.113.301780.
    1. Meloni M., Marchetti M., Garner K., Littlejohns B., Sala-Newby G., Xenophontos N., Floris I., Suleiman M.S., Madeddu P., Caporali A., et al. Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. Mol. Ther. 2013;21:1390–1402. doi: 10.1038/mt.2013.89.
    1. Dentelli P., Rosso A., Orso F., Olgasi C., Taverna D., Brizzi M.F. microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression. Arterioscler. Thromb. Vasc. Biol. 2010;30:1562–1568. doi: 10.1161/ATVBAHA.110.206201.
    1. Liu X., Cheng Y., Zhang S., Lin Y., Yang J., Zhang C. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ. Res. 2009;104:476–487. doi: 10.1161/CIRCRESAHA.108.185363.
    1. Chen Y., Gorski D.H. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood. 2008;111:1217–1226. doi: 10.1182/blood-2007-07-104133.
    1. Sessa R., Seano G., di Blasio L., Gagliardi P.A., Isella C., Medico E., Cotelli F., Bussolino F., Primo L. The miR-126 regulates angiopoietin-1 signaling and vessel maturation by targeting p85β. Biochim. Biophys. Acta. 2012;1823:1925–1935. doi: 10.1016/j.bbamcr.2012.07.011.
    1. Porrello E.R., Mahmoud A.I., Simpson E., Hill J.A., Richardson J.A., Olson E.N., Sadek H.A. Transient regenerative potential of the neonatal mouse heart. Science. 2011;331:1078–1080. doi: 10.1126/science.1200708.
    1. Bergmann O., Bhardwaj R.D., Bernard S., Zdunek S., Barnabe-Heider F., Walsh S., Zupicich J., Alkass K., Buchholz B.A., Druid H., et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324:98–102. doi: 10.1126/science.1164680.
    1. Mollova M., Bersell K., Walsh S., Savla J., Das L.T., Park S.Y., Silberstein L.E., Dos Remedios C.G., Graham D., Colan S., et al. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc. Natl. Acad. Sci. USA. 2013;110:1446–1451. doi: 10.1073/pnas.1214608110.
    1. Porrello E.R., Johnson B.A., Aurora A.B., Simpson E., Nam Y.J., Matkovich S.J., Dorn G.W., II, van Rooij E., Olson E.N. MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circ. Res. 2011;109:670–679. doi: 10.1161/CIRCRESAHA.111.248880.
    1. Chen J., Huang Z.P., Seok H.Y., Ding J., Kataoka M., Zhang Z., Hu X., Wang G., Lin Z., Wang S., et al. miR-17–92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ. Res. 2013;112:1557–1566. doi: 10.1161/CIRCRESAHA.112.300658.
    1. Ieda M., Fu J.D., Delgado-Olguin P., Vedantham V., Hayashi Y., Bruneau B.G., Srivastava D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142:375–386. doi: 10.1016/j.cell.2010.07.002.
    1. Qian L., Huang Y., Spencer C.I., Foley A., Vedantham V., Liu L., Conway S.J., Fu J.D., Srivastava D. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485:593–598. doi: 10.1038/nature11044.
    1. Song K., Nam Y.J., Luo X., Qi X., Tan W., Huang G.N., Acharya A., Smith C.L., Tallquist M.D., Neilson E.G., et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485:599–604. doi: 10.1038/nature11139.
    1. Jayawardena T.M., Egemnazarov B., Finch E.A., Zhang L., Payne J.A., Pandya K., Zhang Z., Rosenberg P., Mirotsou M., Dzau V.J. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ. Res. 2012;110:1465–1473. doi: 10.1161/CIRCRESAHA.112.269035.
    1. Van Solingen C., Seghers L., Bijkerk R., Duijs J.M., Roeten M.K., van Oeveren-Rietdijk A.M., Baelde H.J., Monge M., Vos J.B., de Boer H.C., et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J. Cell. Mol. Med. 2009;13:1577–1585. doi: 10.1111/j.1582-4934.2008.00613.x.
    1. Fish J.E., Santoro M.M., Morton S.U., Yu S., Yeh R.F., Wythe J.D., Ivey K.N., Bruneau B.G., Stainier D.Y., Srivastava D. miR-126 regulates angiogenic signaling and vascular integrity. Dev. Cell. 2008;15:272–284. doi: 10.1016/j.devcel.2008.07.008.
    1. Fleissner F., Jazbutyte V., Fiedler J., Gupta S.K., Yin X., Xu Q., Galuppo P., Kneitz S., Mayr M., Ertl G., et al. Short communication: Asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism. Circ. Res. 2010;107:138–143. doi: 10.1161/CIRCRESAHA.110.216770.
    1. Minami Y., Satoh M., Maesawa C., Takahashi Y., Tabuchi T., Itoh T., Nakamura M. Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease. Eur. J. Clin. Investig. 2009;39:359–367. doi: 10.1111/j.1365-2362.2009.02110.x.
    1. Zhao T., Li J., Chen A.F. MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1. Am. J. Physiol. Endocrinol. Metab. 2010;299:E110–E116. doi: 10.1152/ajpendo.00192.2010.
    1. Miranda K.C., Huynh T., Tay Y., Ang Y.S., Tam W.L., Thomson A.M., Lim B., Rigoutsos I. A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126:1203–1217. doi: 10.1016/j.cell.2006.07.031.
    1. Van Rooij E., Marshall W.S., Olson E.N. Toward microRNA-based therapeutics for heart disease: The sense in antisense. Circ. Res. 2008;103:919–928. doi: 10.1161/CIRCRESAHA.108.183426.
    1. Corsten M.F., Dennert R., Jochems S., Kuznetsova T., Devaux Y., Hofstra L., Wagner D.R., Staessen J.A., Heymans S., Schroen B. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ. Cardiovasc. Genet. 2010;3:499–506. doi: 10.1161/CIRCGENETICS.110.957415.
    1. D’Alessandra Y., Devanna P., Limana F., Straino S., di Carlo A., Brambilla P.G., Rubino M., Carena M.C., Spazzafumo L., de Simone M., et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur. Heart J. 2010;31:2765–2773. doi: 10.1093/eurheartj/ehq167.
    1. Fukushima Y., Nakanishi M., Nonogi H., Goto Y., Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ. J. 2011;75:336–340. doi: 10.1253/circj.CJ-10-0457.
    1. Van Empel V.P., de Windt L.J., da Costa Martins P.A. Circulating miRNAs: Reflecting or affecting cardiovascular disease? Curr. Hypertens. Rep. 2012;14:498–509. doi: 10.1007/s11906-012-0310-7.
    1. Qiang L., Hong L., Ningfu W., Huaihong C., Jing W. Expression of miR-126 and miR-508–5p in endothelial progenitor cells is associated with the prognosis of chronic heart failure patients. Int. J. Cardiol. 2013;168:2082–2088. doi: 10.1016/j.ijcard.2013.01.160.
    1. Zhao Y., Wang W., Han L., Rayburn E.R., Hill D.L., Wang H., Zhang R. Isolation, structural determination, and evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol [20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng. Med. Chem. 2007;3:51–60. doi: 10.2174/157340607779317508.
    1. Foshay K.M., Gallicano G.I. miR-17 family miRNAs are expressed during early mammalian development and regulate stem cell differentiation. Dev. Biol. 2009;326:431–443. doi: 10.1016/j.ydbio.2008.11.016.
    1. Frank D., Gantenberg J., Boomgaarden I., Kuhn C., Will R., Jarr K.U., Eden M., Kramer K., Luedde M., Mairbaurl H., et al. MicroRNA-20a inhibits stress-induced cardiomyocyte apoptosis involving its novel target Egln3/PHD3. J. Mol. Cell. Cardiol. 2012;52:711–717. doi: 10.1016/j.yjmcc.2011.12.001.
    1. Wang K.C., Garmire L.X., Young A., Nguyen P., Trinh A., Subramaniam S., Wang N., Shyy J.Y., Li Y.S., Chien S. Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc. Natl. Acad. Sci. USA. 2010;107:3234–3239. doi: 10.1073/pnas.0914825107.
    1. Deacon D.C., Nevis K.R., Cashman T.J., Zhou Y., Zhao L., Washko D., Guner-Ataman B., Burns C.G., Burns C.E. The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development. 2010;137:1887–1896. doi: 10.1242/dev.050526.
    1. Li X., Kong M., Jiang D., Qian J., Duan Q., Dong A. MicroRNA-150 aggravates H2O2-induced cardiac myocyte injury by down-regulating c-myb gene. Acta Biochim. Biophys. Sin. 2013;45:734–741. doi: 10.1093/abbs/gmt067.
    1. Lin Z., Murtaza I., Wang K., Jiao J., Gao J., Li P.F. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc. Natl. Acad. Sci. USA. 2009;106:12103–12108. doi: 10.1073/pnas.0811371106.
    1. Diao X., Shen E., Wang X., Hu B. Differentially expressed microRNAs and their target genes in the hearts of streptozotocin-induced diabetic mice. Mol. Med. Rep. 2011;4:633–640.
    1. Sayed D., Rane S., Lypowy J., He M., Chen I.Y., Vashistha H., Yan L., Malhotra A., Vatner D., Abdellatif M. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol. Biol. Cell. 2008;19:3272–3282. doi: 10.1091/mbc.E08-02-0159.
    1. Van Rooij E., Doevendans P.A., de Theije C.C., Babiker F.A., Molkentin J.D., de Windt L.J. Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy. J. Biol. Chem. 2002;277:48617–48626.
    1. Arron J.R., Winslow M.M., Polleri A., Chang C.P., Wu H., Gao X., Neilson J.R., Chen L., Heit J.J., Kim S.K., et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature. 2006;441:595–600. doi: 10.1038/nature04678.
    1. Song X.W., Li Q., Lin L., Wang X.C., Li D.F., Wang G.K., Ren A.J., Wang Y.R., Qin Y.W., Yuan W.J., et al. MicroRNAs are dynamically regulated in hypertrophic hearts, and miR-199a is essential for the maintenance of cell size in cardiomyocytes. J. Cell. Physiol. 2010;225:437–443. doi: 10.1002/jcp.22217.
    1. Rane S., He M., Sayed D., Vashistha H., Malhotra A., Sadoshima J., Vatner D.E., Vatner S.F., Abdellatif M. Downregulation of miR-199a derepresses hypoxia-inducible factor-1α and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ. Res. 2009;104:879–886. doi: 10.1161/CIRCRESAHA.108.193102.
    1. Ikeda S., He A., Kong S.W., Lu J., Bejar R., Bodyak N., Lee K.H., Ma Q., Kang P.M., Golub T.R., et al. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol. Cell Biol. 2009;29:2193–2204. doi: 10.1128/MCB.01222-08.
    1. Zhang Z.H., Li J., Liu B.R., Luo C.F., Dong Q., Zhao L.N., Zhong Y., Chen W.Y., Chen M.S., Liu S.M. MicroRNA-26 was decreased in rat cardiac hypertrophy model and may be a promising therapeutic target. J. Cardiovasc. Pharmacol. 2013;62:312–319. doi: 10.1097/FJC.0b013e31829b82e6.
    1. Wang J., Song Y., Zhang Y., Xiao H., Sun Q., Hou N., Guo S., Wang Y., Fan K., Zhan D., et al. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice. Cell Res. 2012;22:516–527. doi: 10.1038/cr.2011.132.
    1. Boettger T., Beetz N., Kostin S., Schneider J., Kruger M., Hein L., Braun T. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J. Clin. Investig. 2009;119:2634–2647. doi: 10.1172/JCI38864.
    1. Care A., Catalucci D., Felicetti F., Bonci D., Addario A., Gallo P., Bang M.L., Segnalini P., Gu Y., Dalton N.D., et al. MicroRNA-133 controls cardiac hypertrophy. Nat. Med. 2007;13:613–618. doi: 10.1038/nm1582.
    1. Luo X., Xiao J., Lin H., Li B., Lu Y., Yang B., Wang Z. Transcriptional activation by stimulating protein 1 and post-transcriptional repression by muscle-specific microRNAs of IKs-encoding genes and potential implications in regional heterogeneity of their expressions. J. Cell. Physiol. 2007;212:358–367. doi: 10.1002/jcp.21030.
    1. Yin V.P., Lepilina A., Smith A., Poss K.D. Regulation of zebrafish heart regeneration by miR-133. Dev. Biol. 2012;365:319–327. doi: 10.1016/j.ydbio.2012.02.018.
    1. Hu S., Huang M., Nguyen P.K., Gong Y., Li Z., Jia F., Lan F., Liu J., Nag D., Robbins R.C., et al. Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation. Circulation. 2011;124:S27–S34. doi: 10.1161/CIRCULATIONAHA.111.017954.
    1. Jakob P., Landmesser U. Role of microRNAs in stem/progenitor cells and cardiovascular repair. Cardiovasc. Res. 2012;93:614–622. doi: 10.1093/cvr/cvr311.

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