1887
Volume 2014, Issue 2
  • ISSN: 2305-7823
  •  E-ISSN:  Will be obtained soon

Abstract

MicroRNAs (miRNAs) have emerged as potent modulators of mammalian gene expression, thereby broadening the spectrum of molecular mechanisms orchestrating human physiological and pathological cellular functions. Growing evidence suggests that these small non-coding RNA molecules are pivotal regulators of cardiovascular development and disease. Importantly, multiple miRNAs have been specifically implicated in the onset and progression of heart failure, thus providing a new platform for battling this multi-faceted disease. This review introduces the basic concepts of miRNA biology, describes representative examples of miRNAs associated with multiple aspects of HF pathogenesis, and explores the prognostic, diagnostic and therapeutic potential of miRNAs in the cardiology clinic.

Loading

Article metrics loading...

/content/journals/10.5339/gcsp.2014.30
2014-10-01
2020-05-26
Loading full text...

Full text loading...

/deliver/fulltext/gcsp/2014/2/gcsp.2014.30.html?itemId=/content/journals/10.5339/gcsp.2014.30&mimeType=html&fmt=ahah

References

  1. McMurray JJ, Pfeffer MA. Heart failure. Lancet. May 28-Jun 3 2005; 365:9474:18771889.
    [Google Scholar]
  2. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. Jan 1 2013; 127:1:e6e245.
    [Google Scholar]
  3. Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival in a community-based population. JAMA. Jul 21 2004; 292:3:344350.
    [Google Scholar]
  4. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, Murabito JM, Vasan RS. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. Oct 31 2002; 347:18:13971402.
    [Google Scholar]
  5. Matsushita K, Blecker S, Pazin-Filho A, Bertoni A, Chang PP, Coresh J, Selvin E. The association of hemoglobin a1c with incident heart failure among people without diabetes: the atherosclerosis risk in communities study. Diabetes. Aug 2010; 59:8:20202026.
    [Google Scholar]
  6. Meyer T, Pankuweit S, Richter A, Maisch B, Ruppert V. Detection of a large duplication mutation in the myosin-binding protein C3 gene in a case of hypertrophic cardiomyopathy. Gene. Jun 29 2013; 527:1:416420.
    [Google Scholar]
  7. Liu Y, Bai R, Wang L, Zhang C, Zhao R, Wan D, Chen X, Caceres G, Barr D, Barajas-Martinez H, Antzelevitch C, Hu D. Identification of a novel de novo mutation associated with PRKAG2 cardiac syndrome and early onset of heart failure. PLoS One. 2013; 8:5:e64603.
    [Google Scholar]
  8. Arvanitis DA, Sanoudou D, Kolokathis F, Vafiadaki E, Papalouka V, Kontrogianni-Konstantopoulos A, Theodorakis GN, Paraskevaidis IA, Adamopoulos S, Dorn GW 2nd, Kremastinos DT, Kranias EG. The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy. Eur Heart J. Oct 2008; 29:20:25142525.
    [Google Scholar]
  9. Dorn GW 2nd. The genomic architecture of sporadic heart failure. Circ Res. May 13 2011; 108:10:12701283.
    [Google Scholar]
  10. Kalozoumi G, Tzimas C, Sanoudou D. The expanding role of epigenetics. Global Cardiology Science and Practice. 2012; 2012:1.
    [Google Scholar]
  11. Smalheiser NR. EST analyses predict the existence of a population of chimeric microRNA precursor-mRNA transcripts expressed in normal human and mouse tissues. Genome Biol. 2003; 4:7:403.
    [Google Scholar]
  12. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. Dec 2004; 10:12:19571966.
    [Google Scholar]
  13. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. Sep 25 2003; 425:6956:415419.
    [Google Scholar]
  14. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. Jan 2 2004; 303:5654:9598.
    [Google Scholar]
  15. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. Dec 15 2003; 17:24:30113016.
    [Google Scholar]
  16. Sontheimer EJ. Assembly and function of RNA silencing complexes. Nat Rev Mol Cell Biol. Feb 2005; 6:2:127138.
    [Google Scholar]
  17. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. Oct 17 2003; 115:2:199208.
    [Google Scholar]
  18. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell. Oct 17 2003; 115:2:209216.
    [Google Scholar]
  19. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. Nov 18 2005; 123:4:631640.
    [Google Scholar]
  20. Ambros V. The functions of animal microRNAs. Nature. Sep 16 2004; 431:7006:350355.
    [Google Scholar]
  21. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. Sep 20 2; 297:5589:20562060.
    [Google Scholar]
  22. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. Jan 23 2004; 116:2:281297.
    [Google Scholar]
  23. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. Jan 14 2005; 120:1:1520.
    [Google Scholar]
  24. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. Sep 22 2006; 126:6:12031217.
    [Google Scholar]
  25. Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. Jan 14 2005; 120:1:2124.
    [Google Scholar]
  26. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. Jul 2005; 37:7:766770.
    [Google Scholar]
  27. Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. Oct 2006; 11:4:441450.
    [Google Scholar]
  28. Townley-Tilson WH, Callis TE, Wang D. MicroRNAs 1, 133, and 206: critical factors of skeletal and cardiac muscle development, function, and disease. Int J Biochem Cell Biol. Aug 2010; 42:8:12521255.
    [Google Scholar]
  29. Dorn GW 2nd. MicroRNAs in cardiac disease. Transl Res. Apr 2011; 157:4:226235.
    [Google Scholar]
  30. Ono K, Kuwabara Y, Han J. MicroRNAs and cardiovascular diseases. FEBS J. May 2011; 278:10:16191633.
    [Google Scholar]
  31. Boettger T, Braun T. A new level of complexity: the role of microRNAs in cardiovascular development. Circ Res. Mar 30 2012; 110:7:10001013.
    [Google Scholar]
  32. Dangwal S, Bang C, Thum T. Novel techniques and targets in cardiovascular microRNA research. Cardiovasc Res. Mar 15 2012; 93:4:545554.
    [Google Scholar]
  33. Leptidis S, El Azzouzi H, Lok SI, de Weger R, Olieslagers S, Kisters N, Silva GJ, Heymans S, Cuppen E, Berezikov E, De Windt LJ, da Costa Martins P. A deep sequencing approach to uncover the miRNOME in the human heart. PLoS One. 2013; 8:2:e57800.
    [Google Scholar]
  34. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ. Dicer is essential for mouse development. Nat Genet. Nov 2003; 35:3:215217.
    [Google Scholar]
  35. Wienholds E, Koudijs MJ, van Eeden FJ, Cuppen E, Plasterk RH. The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet. Nov 2003; 35:3:217218.
    [Google Scholar]
  36. Yang WJ, Yang DD, Na S, Sandusky GE, Zhang Q, Zhao G. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem. Mar 11 2005; 280:10:93309335.
    [Google Scholar]
  37. Otsuka M, Zheng M, Hayashi M, Lee JD, Yoshino O, Lin S, Han J. Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest. May 2008; 118:5:19441954.
    [Google Scholar]
  38. Huang ZP, Chen JF, Regan JN, Maguire CT, Tang RH, Dong XR, Majesky MW, Wang DZ. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. Dec 2010; 30:12:25752586.
    [Google Scholar]
  39. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF. MicroRNAs regulate brain morphogenesis in zebrafish. Science. May 6 2005; 308:5723:833838.
    [Google Scholar]
  40. Lagendijk AK, Goumans MJ, Burkhard SB, Bakkers J. MicroRNA-23 restricts cardiac valve formation by inhibiting Has2 and extracellular hyaluronic acid production. Circ Res. Sep 2 2011; 109:6:649657.
    [Google Scholar]
  41. Saxena A, Tabin CJ. miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation. Proc Natl Acad Sci U S A. Jan 5 2010; 107:1:8791.
    [Google Scholar]
  42. Singh MK, Lu MM, Massera D, Epstein JA. MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development. J Biol Chem. Nov 25 2011; 286:47:4103641045.
    [Google Scholar]
  43. da Costa Martins PA, Bourajjaj M, Gladka M, Kortland M, van Oort RJ, Pinto YM, Molkentin JD, De Windt LJ. Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation. Oct 7 2008; 118:15:15671576.
    [Google Scholar]
  44. Kalsotra A, Wang K, Li PF, Cooper TA. MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes Dev. Apr 1 2010; 24:7:653658.
    [Google Scholar]
  45. Malizia AP, Wang DZ. MicroRNAs in cardiomyocyte development. Wiley Interdiscip Rev Syst Biol Med. Mar-Apr 2011; 3:2:183190.
    [Google Scholar]
  46. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. Jul 14 2005; 436:7048:214220.
    [Google Scholar]
  47. 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 Genet. Feb 2006; 38:2:228233.
    [Google Scholar]
  48. McFadden DG, Barbosa AC, Richardson JA, Schneider MD, Srivastava D, Olson EN. The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner. Development. Jan 2005; 132:1:189201.
    [Google Scholar]
  49. Srivastava D, Cserjesi P, Olson EN. A subclass of bHLH proteins required for cardiac morphogenesis. Science. Dec 22 1995; 270:5244:19951999.
    [Google Scholar]
  50. Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. Jun 1997; 16:2:154160.
    [Google Scholar]
  51. Yamagishi H, Yamagishi C, Nakagawa O, Harvey RP, Olson EN, Srivastava D. The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol. Nov 15 2001; 239:2:190203.
    [Google Scholar]
  52. Yelon D, Ticho B, Halpern ME, Ruvinsky I, Ho RK, Silver LM, Stainier DY. The bHLH transcription factor hand2 plays parallel roles in zebrafish heart and pectoral fin development. Development. Jun 2000; 127:12:25732582.
    [Google Scholar]
  53. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. Apr 20 2007; 129:2:303317.
    [Google Scholar]
  54. Niu Z, Li A, Zhang SX, Schwartz RJ. Serum response factor micromanaging cardiogenesis. Curr Opin Cell Biol. Dec 2007; 19:6:618627.
    [Google Scholar]
  55. Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, Olson EN. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. Dec 1 2008; 22:23:32423254.
    [Google Scholar]
  56. Cao X, Wang J, Wang Z, Du J, Yuan X, Huang W, Meng J, Gu H, Nie Y, Ji B, Hu S, Zheng Z. MicroRNA profiling during rat ventricular maturation: A role for miR-29a in regulating cardiomyocyte cell cycle re-entry. FEBS Lett. May 21 2013; 587:10:15481555.
    [Google Scholar]
  57. Chinchilla A, Lozano E, Daimi H, Esteban FJ, Crist C, Aranega AE, Franco D. MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression. Cardiovasc Res. Jan 1 2011; 89:1:98108.
    [Google Scholar]
  58. Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY, Kida YS, Ueki Y, Nagayama K, Kawakami K, Matsumoto T, Sato M, Ogura T. Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat Commun. Jun 10 2013; 4::1978.
    [Google Scholar]
  59. Morton SU, Scherz PJ, Cordes KR, Ivey KN, Stainier DY, Srivastava D. microRNA-138 modulates cardiac patterning during embryonic development. Proc Natl Acad Sci U S A. Nov 18 2008; 105:46:1783017835.
    [Google Scholar]
  60. Chiavacci E, Dolfi L, Verduci L, Meghini F, Gestri G, Evangelista AM, Wilson SW, Cremisi F, Pitto L. MicroRNA 218 mediates the effects of Tbx5a over-expression on zebrafish heart development. PLoS One. 2012; 7:11:e50536.
    [Google Scholar]
  61. Fish JE, Wythe JD, Xiao T, Bruneau BG, Stainier DY, Srivastava D, Woo S. A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish. Development. Apr 2011; 138:7:14091419.
    [Google Scholar]
  62. Kochegarov A, Moses A, Lian W, Meyer J, Hanna MC, Lemanski LF. A new unique form of microRNA from human heart, microRNA-499c, promotes myofibril formation and rescues cardiac development in mutant axolotl embryos. J Biomed Sci. 2013; 20::20.
    [Google Scholar]
  63. Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J, Willis MS, Selzman CH, Wang DZ. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest. Sep 2009; 119:9:27722786.
    [Google Scholar]
  64. Wilson KD, Hu S, Venkatasubrahmanyam S, Fu JD, Sun N, Abilez OJ, Baugh JJ, Jia F, Ghosh Z, Li RA, Butte AJ, Wu JC. Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet. Oct 2010; 3:5:426435.
    [Google Scholar]
  65. Olson EN. Gene regulatory networks in the evolution and development of the heart. Science. Sep 29 2006; 313:5795:19221927.
    [Google Scholar]
  66. Molkentin JD, Lin Q, Duncan SA, Olson EN. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. Apr 15 1997; 11:8:10611072.
    [Google Scholar]
  67. Fu JD, Rushing SN, Lieu DK, Chan CW, Kong CW, Geng L, Wilson KD, Chiamvimonvat N, Boheler KR, Wu JC, Keller G, Hajjar RJ, Li RA. Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PLoS One. 2011; 6:11:e27417.
    [Google Scholar]
  68. Sucharov C, Bristow MR, Port JD. miRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol. Aug 2008; 45:2:185192.
    [Google Scholar]
  69. Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD, Golub TR, Pieske B, Pu WT. Altered microRNA expression in human heart disease. Physiol Genomics. Nov 14 2007; 31:3:367373.
    [Google Scholar]
  70. 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 U S A. Nov 28 2006; 103:48:1825518260.
    [Google Scholar]
  71. Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo MA, Cimino V, De Marinis L, Frustaci A, Catalucci D, Condorelli G. 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. Dec 8 2009; 120:23:23772385.
    [Google Scholar]
  72. Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR, Pu WT. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol. Apr 2009; 29:8:21932204.
    [Google Scholar]
  73. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Høydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G. MicroRNA-133 controls cardiac hypertrophy. Nat Med. May 2007; 13:5:613618.
    [Google Scholar]
  74. Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. Feb 16 2007; 100:3:416424.
    [Google Scholar]
  75. Bagnall RD, Tsoutsman T, Shephard RE, Ritchie W, Semsarian C. Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure. PLoS One. 2012; 7:9:e44744.
    [Google Scholar]
  76. Ali R, Huang Y, Maher SE, Kim RW, Giordano FJ, Tellides G, Geirsson A. miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling. J Mol Cell Cardiol. May 2012; 52:5:10271037.
    [Google Scholar]
  77. van Almen GC, Verhesen W, van Leeuwen RE, van de Vrie M, Eurlings C, Schellings MW, Swinnen M, Cleutjens JP, van Zandvoort MA, Heymans S, Schroen B. MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell. Oct 2011; 10:5:769779.
    [Google Scholar]
  78. Matkovich SJ, Van Booven DJ, Youker KA, Torre-Amione G, Diwan A, Eschenbacher WH, Dorn LE, Watson MA, Margulies KB, Dorn GW 2nd. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation. Mar 10 2009; 119:9:12631271.
    [Google Scholar]
  79. 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. Circulation. Jul 17 2007; 116:3:258267.
    [Google Scholar]
  80. Lin Z, Murtaza I, Wang K, Jiao J, Gao J, Li PF. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc Natl Acad Sci U S A. Jul 21 2009; 106:29:1210312108.
    [Google Scholar]
  81. Wang K, Lin ZQ, Long B, Li JH, Zhou J, Li PF. Cardiac hypertrophy is positively regulated by MicroRNA miR-23a. J Biol Chem. Jan 2 2012; 287:1:589599.
    [Google Scholar]
  82. Wang J, Huang W, Xu R, Nie Y, Cao X, Meng J, Xu X, Hu S, Zheng Z. MicroRNA-24 regulates cardiac fibrosis after myocardial infarction. J Cell Mol Med. Sep 2012; 16:9:21502160.
    [Google Scholar]
  83. Matkovich SJ, Wang W, Tu Y, Eschenbacher WH, Dorn LE, Condorelli G, Diwan A, Nerbonne JM, Dorn GW 2nd. MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res. Jan 8 2010; 106:1:166175.
    [Google Scholar]
  84. 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. Nature. Dec 18 2008; 456:7224:980984.
    [Google Scholar]
  85. Choy MK, Movassagh M, Siggens L, Vujic A, Goddard M, Sánchez A, Perkins N, Figg N, Bennett M, Carroll J, Foo R. High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-kappaB-complex-dependent gene expression in human heart failure. Genome Med. 2010; 2:6:37.
    [Google Scholar]
  86. Wei C, Kim IK, Kumar S, Jayasinghe S, Hong N, Castoldi G, Catalucci D, Jones WK, Gupta S. NF-kappaB mediated miR-26a regulation in cardiac fibrosis. J Cell Physiol. Jul 2013; 228:7:14331442.
    [Google Scholar]
  87. 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 U S A. Sep 2 2008; 105:35:1302713032.
    [Google Scholar]
  88. Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, Herias V, van Leeuwen RE, Schellings MW, Barenbrug P, Maessen JG, Heymans S, Pinto YM, Creemers EE. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. Jan 30 2009; 104:2:170178, 176p following 178.
    [Google Scholar]
  89. Creemers EE, Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. Cardiovasc Res. Feb 1 2011; 89:2:265272.
    [Google Scholar]
  90. Wang C, Wang S, Zhao P, Wang X, Wang J, Wang Y, Song L, Zou Y, Hui R. MiR-221 promotes cardiac hypertrophy in vitro through the modulation of p27 expression. J Cell Biochem. Jun 2012; 113:6:20402046.
    [Google Scholar]
  91. Zhang HB, Li RC, Xu M, Lai YS, Wu HD, Xie XJ, Gao W, Ye H, Zhang YY, Meng X, Wang SQ. Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure. Cardiovasc Res. May 1 2013; 98:2:269276.
    [Google Scholar]
  92. 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. Science. Apr 27 2007; 316:5824:575579.
    [Google Scholar]
  93. Busk PK, Cirera S. MicroRNA profiling in early hypertrophic growth of the left ventricle in rats. Biochem Biophys Res Commun. Jun 11 2010; 396:4:989993.
    [Google Scholar]
  94. Belevych AE, Sansom SE, Terentyeva R, Ho HT, Nishijima Y, Martin MM, Jindal HK, Rochira JA, Kunitomo Y, Abdellatif M, Carnes CA, Elton TS, Györke S, Terentyev D. MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS One. 2011; 6:12:e28324.
    [Google Scholar]
  95. Janse MJ. Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc Res. Feb 1 2004; 61:2:208217.
    [Google Scholar]
  96. Pogwizd SM, Bers DM. Cellular basis of triggered arrhythmias in heart failure. Trends Cardiovasc Med. Feb 2004; 14:2:6166.
    [Google Scholar]
  97. Tsoutsman T, Kelly M, Ng DC, Tan JE, Tu E, Lam L, Bogoyevitch MA, Seidman CE, Seidman JG, Semsarian C. Severe heart failure and early mortality in a double-mutation mouse model of familial hypertrophic cardiomyopathy. Circulation. Apr 8 2008; 117:14:18201831.
    [Google Scholar]
  98. Cheng Y, Ji R, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol. Jun 2007; 170:6:18311840.
    [Google Scholar]
  99. Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, Rojas M, Hammond SM, Wang DZ. Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J Mol Cell Cardiol. Jun 2007; 42:6:11371141.
    [Google Scholar]
  100. Reddy S, Zhao M, Hu DQ, Fajardo G, Hu S, Ghosh Z, Rajagopalan V, Wu JC, Bernstein D. Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. Physiol Genomics. May 1 2012; 44:10:562575.
    [Google Scholar]
  101. Zhao M, Chow A, Powers J, Fajardo G, Bernstein D. Microarray analysis of gene expression after transverse aortic constriction in mice. Physiol Genomics. Sep 16 2004; 19:1:93105.
    [Google Scholar]
  102. Kaufman BD, Desai M, Reddy S, Osorio JC, Chen JM, Mosca RS, Ferrante AW, Mital S. Genomic profiling of left and right ventricular hypertrophy in congenital heart disease. J Card Fail. Nov 2008; 14:9:760767.
    [Google Scholar]
  103. Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, Remke J, Caprio M, Jentzsch C, Engelhardt S, Geisendorf S, Glas C, Hofmann TG, Nessling M, Richter K, Schiffer M, Carrier L, Napp LC, Bauersachs J, Chowdhury K, Thum T. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat Commun. 2012; 3::1078.
    [Google Scholar]
  104. Willis MS, Ike C, Li L, Wang DZ, Glass DJ, Patterson C. Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo. Circ Res. Mar 2 2007; 100:4:456459.
    [Google Scholar]
  105. Wang J, Song Y, Zhang Y, Xiao H, Sun Q, Hou N, Guo S, Wang Y, Fan K, Zhan D, Zha L, Cao Y, Li Z, Cheng X, Zhang Y, Yang X. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice. Cell Res. Mar 2012; 22:3:516527.
    [Google Scholar]
  106. Nagalingam RS, Sundaresan NR, Gupta MP, Geenen DL, Solaro RJ, Gupta M. A cardiac-enriched microRNA, miR-378, blocks cardiac hypertrophy by targeting Ras signaling. J Biol Chem. Apr 19 2013; 288:16:1121611232.
    [Google Scholar]
  107. Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ, Nagalingam RS, Gupta M. A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival. J Biol Chem. Apr 13 2012; 287:16:1291312926.
    [Google Scholar]
  108. Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S, Leierseder S, Loyer X, Giacca M, Zentilin L, Thum T, Laggerbauer B, Engelhardt S. MiR-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors. Circulation. May 28 2013; 127:21:20972106.
    [Google Scholar]
  109. Wang K, Long B, Zhou J, Li PF. miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy. J Biol Chem. Apr 16 2010; 285:16:1190311912.
    [Google Scholar]
  110. Souders CA, Bowers SL, Baudino TA. Cardiac fibroblast: the renaissance cell. Circ Res. Dec 4 2009; 105:12:11641176.
    [Google Scholar]
  111. Jugdutt BI. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation. Sep 16 2003; 108:11:13951403.
    [Google Scholar]
  112. Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, Gnyawali S, Shilo S, Nuovo GJ, Sen CK. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res. Apr 1 2009; 82:1:2129.
    [Google Scholar]
  113. Liang H, Zhang C, Ban T, Liu Y, Mei L, Piao X, Zhao D, Lu Y, Chu W, Yang B. A novel reciprocal loop between microRNA-21 and TGFbetaRIII is involved in cardiac fibrosis. Int J Biochem Cell Biol. Dec 2012; 44:12:21522160.
    [Google Scholar]
  114. Wada AM, Smith TK, Osler ME, Reese DE, Bader DM. Epicardial/Mesothelial cell line retains vasculogenic potential of embryonic epicardium. Circ Res. Mar 21 2003; 92:5:525531.
    [Google Scholar]
  115. Di Meglio F, Castaldo C, Nurzynska D, Romano V, Miraglia R, Bancone C, Langella G, Vosa C, Montagnani S. Epithelial-mesenchymal transition of epicardial mesothelium is a source of cardiac CD117-positive stem cells in adult human heart. J Mol Cell Cardiol. Nov 2010; 49:5:719727.
    [Google Scholar]
  116. Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. Jan 11 2007; 445:7124:177182.
    [Google Scholar]
  117. Russell JL, Goetsch SC, Gaiano NR, Hill JA, Olson EN, Schneider JW. A dynamic notch injury response activates epicardium and contributes to fibrosis repair. Circ Res. Jan 7 2011; 108:1:5159.
    [Google Scholar]
  118. van Tuyn J, Atsma DE, Winter EM, van der Velde-van Dijke I, Pijnappels DA, Bax NA, Knaän-Shanzer S, Gittenberger-de Groot AC, Poelmann RE, van der Laarse A, van der Wall EE, Schalij MJ, de Vries AA. Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro. Stem Cells. Feb 2007; 25:2:271278.
    [Google Scholar]
  119. Bronnum H, Andersen DC, Schneider M, Sandberg MB, Eskildsen T, Nielsen SB, Kalluri R, Sheikh SP. miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1. PLoS One. 2013; 8:2:e56280.
    [Google Scholar]
  120. Bronnum H, Andersen DC, Schneider M, Nossent AY, Nielsen SB, Sheikh SP. Islet-1 is a dual regulator of fibrogenic epithelial-to-mesenchymal transition in epicardial mesothelial cells. Exp Cell Res. Feb 15 2013; 319:4:424435.
    [Google Scholar]
  121. Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol. Nov 2010; 225:3:631637.
    [Google Scholar]
  122. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. Aug 2007; 13:8:952961.
    [Google Scholar]
  123. Ghosh AK, Nagpal V, Covington JW, Michaels MA, Vaughan DE. Molecular basis of cardiac endothelial-to-mesenchymal transition (EndMT): differential expression of microRNAs during EndMT. Cell Signal. May 2012; 24:5:10311036.
    [Google Scholar]
  124. Ghosh AK, Vaughan DE. Fibrosis: is it a coactivator disease? Front Biosci (Elite Ed). 2012; 4::15561570.
    [Google Scholar]
  125. Terentyev D, Belevych AE, Terentyeva R, Martin MM, Malana GE, Kuhn DE, Abdellatif M, Feldman DS, Elton TS, Györke S. miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2. Circ Res. Feb 27 2009; 104:4:514521.
    [Google Scholar]
  126. Tritsch E, Mallat Y, Lefebvre F, Diguet N, Escoubet B, Blanc J, De Windt LJ, Catalucci D, Vandecasteele G, Li Z, Mericskay M. An SRF/miR-1 axis regulates NCX1 and Annexin A5 protein levels in the normal and failing heart. Cardiovasc Res. Jun 1 2013; 98:3:372380.
    [Google Scholar]
  127. Kumarswamy R, Lyon AR, Volkmann I, Mills AM, Bretthauer J, Pahuja A, Geers-Knörr C, Kraft T, Hajjar RJ, Macleod KT, Harding SE, Thum T. SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway. Eur Heart J. May 2012; 33:9:10671075.
    [Google Scholar]
  128. Braunwald E. Biomarkers in heart failure. N Engl J Med. May 15 2008; 358:20:21482159.
    [Google Scholar]
  129. Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. Feb 2012; 14:2:147154.
    [Google Scholar]
  130. Fan KL, Zhang HF, Shen J, Zhang Q, Li XL. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J. Jan-Feb 2013; 65:1:1216.
    [Google Scholar]
  131. Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M, Kitamura T, Hamasaki T, Nanto S, Kawahara Y, Komuro I. Circulating p53-Responsive MicroRNAs Are Predictive Indicators of Heart Failure After Acute Myocardial Infarction. Circ Res. Jul 19 2013; 113:3:322326.
    [Google Scholar]
  132. 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. Oct 3 2013; 168:3:20822088.
    [Google Scholar]
  133. Dickinson BA, Semus HM, Montgomery RL, Stack C, Latimer PA, Lewton SM, Lynch JM, Hullinger TG, Seto AG, van Rooij E. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure. Eur J Heart Fail. Jun 2013; 15:6:650659.
    [Google Scholar]
  134. Voellenkle C, van Rooij J, Cappuzzello C, Greco S, Arcelli D, Di Vito L, Melillo G, Rigolini R, Costa E, Crea F, Capogrossi MC, Napolitano M, Martelli F. MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genomics. Aug 2010; 42:3:420426.
    [Google Scholar]
  135. Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J. 2011; 75:2:336340.
    [Google Scholar]
  136. 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 Res. Sep 3 2010; 107:5:677684.
    [Google Scholar]
  137. Cogoni C, Macino G. Post-transcriptional gene silencing across kingdoms. Curr Opin Genet Dev. Dec 2000; 10:6:638643.
    [Google Scholar]
  138. Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. Aug 29 2013; 369:9:819829.
    [Google Scholar]
  139. Crunkhorn S. Trial watch: pioneering RNAi therapy shows antitumour activity in humans. Nat Rev Drug Discov. Mar 2013; 12:3:178.
    [Google Scholar]
  140. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, Hutabarat RM, Clausen VA, Karsten V, Cehelsky J, Nochur SV, Kotelianski V, Horton J, Mant T, Chiesa J, Ritter J, Munisamy M, Vaishnaw AK, Gollob JA, Simon A. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. Jan 4 2014; 383:9911:6068.
    [Google Scholar]
  141. Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. Dec 3 2001; 20:23:68776888.
    [Google Scholar]
  142. Bartlett DW, Davis ME. Effect of siRNA nuclease stability on the in vitro and in vivo kinetics of siRNA-mediated gene silencing. Biotechnol Bioeng. Jul 1 2007; 97:4:909921.
    [Google Scholar]
  143. Aagaard L, Rossi JJ. RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev. Mar 30 2007; 59:2–3:7586.
    [Google Scholar]
  144. Xia H, Mao Q, Paulson HL, Davidson BL. siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol. Oct 2002; 20:10:10061010.
    [Google Scholar]
  145. Ye K, Malinina L, Patel DJ. Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature. Dec 18 2003; 426:6968:874878.
    [Google Scholar]
  146. Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskämper J, Westermann D, Bisping E, Ly H, Wang X, Kawase Y, Chen J, Liang L, Sipo I, Vetter R, Weger S, Kurreck J, Erdmann V, Tschope C, Pieske B, Lebeche D, Schultheiss HP, Hajjar RJ, Poller WC. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation. Mar 10 2009; 119:9:12411252.
    [Google Scholar]
  147. Kranias EG, Hajjar RJ. Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome. Circ Res. Jun 8 2012; 110:12:16461660.
    [Google Scholar]
  148. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. Feb 28 2003; 299:5611:14101413.
    [Google Scholar]
  149. Zhang HS, Liu D, Huang Y, Schmidt S, Hickey R, Guschin D, Su H, Jovin IS, Kunis M, Hinkley S, Liang Y, Hinh L, Spratt SK, Case CC, Rebar EJ, Ehrlich BE, Gregory PD, Giordano FJ. A designed zinc-finger transcriptional repressor of phospholamban improves function of the failing heart. Mol Ther. Aug 2012; 20:8:15081515.
    [Google Scholar]
  150. Iwanaga Y, Hoshijima M, Gu Y, Iwatate M, Dieterle T, Ikeda Y, Date MO, Chrast J, Matsuzaki M, Peterson KL, Chien KR, Ross J Jr. Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest. Mar 2004; 113:5:727736.
    [Google Scholar]
  151. Fechner H, Suckau L, Kurreck J, Sipo I, Wang X, Pinkert S, Loschen S, Rekittke J, Weger S, Dekkers D, Vetter R, Erdmann VA, Schultheiss HP, Paul M, Lamers J, Poller W. Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban. Gene Ther. Feb 2007; 14:3:211218.
    [Google Scholar]
  152. Eizema K, Fechner H, Bezstarosti K, Schneider-Rasp S, van der Laarse A, Wang H, Schultheiss HP, Poller WC, Lamers JM. Adenovirus-based phospholamban antisense expression as a novel approach to improve cardiac contractile dysfunction: comparison of a constitutive viral versus an endothelin-1-responsive cardiac promoter. Circulation. May 9 2000; 101:18:21932199.
    [Google Scholar]
  153. Andino LM, Takeda M, Kasahara H, Jakymiw A, Byrne BJ, Lewin AS. AAV-mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes. J Gene Med. Feb 2008; 10:2:132142.
    [Google Scholar]
  154. Miyazaki Y, Ikeda Y, Shiraishi K, Fujimoto SN, Aoyama H, Yoshimura K, Inui M, Hoshijima M, Kasahara H, Aoki H, Matsuzaki M. Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling. PLoS One. 2012; 7:4:e35875.
    [Google Scholar]
  155. Carr AN, Schmidt AG, Suzuki Y, del Monte F, Sato Y, Lanner C, Breeden K, Jing SL, Allen PB, Greengard P, Yatani A, Hoit BD, Grupp IL, Hajjar RJ, DePaoli-Roach AA, Kranias EG. Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol. Jun 2002; 22:12:41244135.
    [Google Scholar]
  156. El-Armouche A, Pamminger T, Ditz D, Zolk O, Eschenhagen T. Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts. Cardiovasc Res. Jan 1 2004; 61:1:8793.
    [Google Scholar]
  157. Dowler T, Bergeron D, Tedeschi AL, Paquet L, Ferrari N, Damha MJ. Improvements in siRNA properties mediated by 2(-deoxy-2(-fluoro-beta-D-arabinonucleic acid (FANA). Nucleic Acids Res. 2006; 34:6:16691675.
    [Google Scholar]
  158. Czauderna F, Fechtner M, Dames S, Aygün H, Klippel A, Pronk GJ, Giese K, Kaufmann J. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. Jun 1 2003; 31:11:27052716.
    [Google Scholar]
  159. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. May 24 2001; 411:6836:494498.
    [Google Scholar]
  160. Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BR. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. Sep 2003; 5:9:834839.
    [Google Scholar]
  161. Tabernero J, Shapiro GI, LoRusso PM, Cervantes A, Schwartz GK, Weiss GJ, Paz-Ares L, Cho DC, Infante JR, Alsina M, Gounder MM, Falzone R, Harrop J, White AC, Toudjarska I, Bumcrot D, Meyers RE, Hinkle G, Svrzikapa N, Hutabarat RM, Clausen VA, Cehelsky J, Nochur SV, Gamba-Vitalo C, Vaishnaw AK, Sah DW, Gollob JA, Burris HA 3rd. First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. Apr 2013; 3:4:406417.
    [Google Scholar]
  162. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. Apr 15 2010; 464:7291:10671070.
    [Google Scholar]
  163. Weiler J, Hunziker J, Hall J. Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther. Mar 2006; 13:6:496502.
    [Google Scholar]
  164. Hammond SM. MicroRNA therapeutics: a new niche for antisense nucleic acids. Trends Mol Med. Mar 2006; 12:3:99101.
    [Google Scholar]
  165. Latronico MV, Condorelli G. Therapeutic use of microRNAs in myocardial diseases. Curr Heart Fail Rep. Sep 2011; 8:3:193197.
    [Google Scholar]
  166. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. Jun 12 2009; 137:6:10051017.
    [Google Scholar]
  167. 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. Circulation. Oct 4 2011; 124:14:15371547.
    [Google Scholar]
  168. Patrick DM, Montgomery RL, Qi X, Obad S, Kauppinen S, Hill JA, van Rooij E, Olson EN. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest. Nov 2010; 120:11:39123916.
    [Google Scholar]
  169. Thum T, Chau N, Bhat B, Gupta SK, Linsley PS, Bauersachs J, Engelhardt S. Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. J Clin Invest. Feb 2011; 121:2:461462, author reply 462-463.
    [Google Scholar]
  170. Tijsen AJ, Pinto YM, Creemers EE. Non-cardiomyocyte microRNAs in heart failure. Cardiovasc Res. Mar 15 2012; 93:4:573582.
    [Google Scholar]
  171. Ahuja P, Sdek P, MacLellan WR. Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol Rev. Apr 2007; 87:2:521544.
    [Google Scholar]
  172. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J. Evidence for cardiomyocyte renewal in humans. Science. Apr 3 2009; 324:5923:98102.
    [Google Scholar]
  173. Bicknell KA, Coxon CH, Brooks G. Can the cardiomyocyte cell cycle be reprogrammed? J Mol Cell Cardiol. Apr 2007; 42:4:706721.
    [Google Scholar]
  174. Kajstura J, Urbanek K, Perl S, Hosoda T, Zheng H, Ogórek B, Ferreira-Martins J, Goichberg P, Rondon-Clavo C, Sanada F, D'Amario D, Rota M, Del Monte F, Orlic D, Tisdale J, Leri A, Anversa P. Cardiomyogenesis in the adult human heart. Circ Res. Jul 23 2010; 107:2:305315.
    [Google Scholar]
  175. van Amerongen MJ, Engel FB. Features of cardiomyocyte proliferation and its potential for cardiac regeneration. J Cell Mol Med. Dec 2008; 12:6A:22332244.
    [Google Scholar]
  176. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerquin-Kern JL, Lechene CP, Lee RT. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. Jan 17 2013; 493:7432:433436.
    [Google Scholar]
  177. Porrello ER, Johnson BA, Aurora AB, Simpson E, Nam YJ, Matkovich SJ, Dorn GW 2nd, van Rooij E, Olson EN. MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circ Res. Sep 2 2011; 109:6:670679.
    [Google Scholar]
  178. Eulalio A, Mano M, Dal Ferro M, Zentilin L, Sinagra G, Zacchigna S, Giacca M. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. Dec 20 2012; 492:7429:376381.
    [Google Scholar]
  179. Chen J, Huang ZP, Seok HY, Ding J, Kataoka M, Zhang Z, Hu X, Wang G, Lin Z, Wang S, Pu WT, Liao R, Wang DZ. mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res. Jun 7 2013; 112:12:15571566.
    [Google Scholar]
  180. Wahlquist C, Jeong D, Rojas-Munoz A, Kho C, Lee A, Mitsuyama S, van Mil A, Park WJ, Sluijter JP, Doevendans PA, Hajjar RJ, Mercola M. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature. Apr 24 2014; 508:7497:531535.
    [Google Scholar]
  181. Das S, Bedja D, Campbell N, Dunkerly B, Chenna V, Maitra A, Steenbergen C. miR-181c Regulates the Mitochondrial Genome, Bioenergetics, and Propensity for Heart Failure In Vivo. PLoS One. 2014; 9:5:e96820.
    [Google Scholar]
  182. Wijnen WJ, van der Made I, van den Oever S, Hiller M, de Boer BA, Picavet DI, Chatzispyrou IA, Houtkooper RH, Tijsen AJ, Hagoort J, van Veen H, Everts V, Ruijter JM, Pinto YM, Creemers EE. Cardiomyocyte-Specific miRNA-30c Over-Expression Causes Dilated Cardiomyopathy. PLoS One. 2014; 9:5:e96290.
    [Google Scholar]
  183. He F, Lv P, Zhao X, Wang X, Ma X, Meng W, Meng X, Dong S. Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction. Mol Cell Biochem. Sep 2014; 394:1–2:137144.
    [Google Scholar]
  184. Goren Y, Meiri E, Hogan C, Mitchell H, Lebanony D, Salman N, Schliamser JE, Amir O. Relation of reduced expression of MiR-150 in platelets to atrial fibrillation in patients with chronic systolic heart failure. Am J Cardiol. Mar 15 2014; 113:6:976981.
    [Google Scholar]
  185. Condorelli G, Latronico MV, Cavarretta E. microRNAs in cardiovascular diseases current knowledge and the road ahead. J Am Coll Cardiol. Jun 3 2014; 63:21:21772187.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/gcsp.2014.30
Loading
/content/journals/10.5339/gcsp.2014.30
Loading

Data & Media loading...

  • Article Type: Review Article
Keyword(s): biomarkers , heart failure , microRNA and therapeutics
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error