JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (5): 60-65.doi: 10.6040/j.issn.1671-7554.0.2015.039

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Effects of microRNA-133 on end-stage myocardial fibrosis of dilated cardiomyopathy

WANG Yong1, LI Quan2, CHEN Shanliang2, WANG Dong2, YU Jianmin2, LI Min2, LIU Tianqi2   

  1. 1. Weifang Medical College, Weifang 261053, Shandong, China;
    2. Department of Cardiac Surgery, Qianfoshan Hospital Affiliated to Shandong University, Shandong Heart Transplantation and Materials Engineering Technology Research Center, Jinan 250014, Shandong, China
  • Received:2015-01-12 Revised:2015-03-20 Online:2015-05-10 Published:2015-05-10

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Abstract: Objective To investigate the effects of microRNA-133(miR-133) on myocardial fibrosis of dilated cardiomyopathy (DCM). Methods A total of 21 myocardial samples of DCM patients undergoing cardiac transplantation (DCM group) and 10 myocardial samples of brain-dead victims of accidental trauma who had no medical evidence of cardiac disease (control group) were collected. The degrees of myocardial fibrosis were observed with masson staining, and cardiomyocyte apoptosis was determined with TdT-mediated dUTP Nick-End Labeling (TUNEL). Human cardiac fibroblasts were cultured, and miR-133mimic(miR-133a mimic and miR-133b mimic) was transfected into the fibroblasts to investigate the effects of miR-133(miR-133a and miR-133b) on myocardial fibrosis. The mRNA expressions of BCL-2 and miR-133 were detected with RT-PCR, and the protein expression of BCL-2 was evaluated with Western blotting. Results In DCM group, severe myocardial fibrosis and myocardial cell apoptosis were observed, collagen volume fraction (CVF) was increased (left ventricle P<0.01; right ventricle P<0.01), myocardial apoptosis index was higher (left ventricle P<0.05; right ventricle P<0.05), and apoptosis-related protein BCL-2 was increased (P<0.05; right ventricle P<0.05). After miR-133a mimic and miR-133b mimic were transfected into human cardiac fibroblasts, the expression of miR-133a and miR-133b were elevated (P<0.01) and BCL-2 was decreased (P<0.01). Conclusion In myocardial tissues of DCM patients, miR-133 can attenuate the stimulation on cardiac fibroblasts induced by BCL-2, inhibit pathologic proliferation of myocardial fibroblasts, and reduce myocardial fibrosis of DCM.

Key words: microRNA-133, Dilated cardiomyopathy, BCL-2, Myocardial fibrosis

CLC Number: 

  • R542.2
[1] Jefferies JL, Towbin JA. Dilated cardiomyopathy[J]. Lancet, 2010, 375(9716):752-762.
[2] Manabe I, Shindo T, Naqai R. Gene expression in fibroblasts and fibrosis:involvement in cardiac hypertrophy[J]. Circ Res, 2002, 91(12):1103-1113.
[3] Chen JF, Murchison EP, Tang R, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure[J]. Proc Natl Acad Sci U S A, 2008, 105(6):2111-2116.
[4] Wang B, Komers R, Carew R, et al. Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis[J] . J Am Soc Nephrol, 2012, 23(2):252-265.
[5] Wan Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis[J]. Proc Natl Acad Sci U S A, 2008, 105(35):13027-13032.
[6] Zhu H, Fan GC. Role of microRNAs in the reperfused myocardium towards post-infarct remodelling[J]. Cardiovasc Res, 2012, 94(2):284-292.
[7] Mewton N, Liu CY, Croisille P, et al. Assessment of myocardial fibrosis with cardiovascular magnetic resonance[J]. J Am Coll Cardiol, 2011, 57(8):891-903.
[8] Heusch G, Libby P, Gersh B, et al. Cardiovascular remodelling in coronary artery disease and heart failure[J]. The Lancet, 2014, 383(9932):1933-1943.
[9] Schnee JM, Hsueh WA. Angiotensi II, adhesion and cardiac fibrosis[J]. Cardiovasc Res, 2000, 46(2):264-268.
[10] Hong BK, Kwon HM, Byun KH, et al. Apoptosis in dilated cardiomyopathy[J]. Korean J Intern Med, 2000, 15(1):56-64.
[11] Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction[J]. Cardiovasc Res, 2002, 53(1):31-47.
[12] Agocha A, Lee HW, Eghbali-Webb M. Hypoxia regulates basal and induced DNA synthesis and collagen type I production in human cardiac fibroblasts:effects of transforming growth factor-beta1, thyroid hormone, angiotensin II and basic fibroblast growth factor[J]. J Mol Cell Cardiol, 1997, 29(8):2233-2244.
[13] Latif N, Khan MA,Birks E,et al. Upregulation of the Bcl-2 family of proteins in end stage heart failure[J]. J Am Coll Cardiol, 2000, 35(7):1769-1777.
[14] Mayorga M, Bahi N, Ballester M, et al. Bcl-2 is a key factor for cardiac fibroblast resistance to programmed cell death[J]. J Biol Chem, 2004, 279(33):34882-34889.
[15] Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2):281-297.
[16] Carè A, Caralucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy[J]. Nat Med, 2007, 13(5):613-618.
[17] Liu N, Bezprozvannaya S, Williams AH, et al. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart[J]. Genes Dev, 2008, 22(23):3242-3254.
[18] Matkovich SJ, Wang W, Tu Y, et al. microRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts[J]. Circ Res, 2010, 106(1):166-175.
[19] Duisters RF, Tijsen AJ, Schroen B, et al. miR-133 and miR-30 regulate connective tissue growth factor:implications for a role of microRNAs in myocardial matrix remodeling[J]. Circ Res, 2009, 104(2):170-178.
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