Int J Sports Med 2020; 41(07): 475-483
DOI: 10.1055/a-1018-1902
Training & Testing

Inhibiting MicroRNA-497 Improves the Effects of Exercise Training on Myocardial Infarction

Zhenci Li
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Jing Lv
2   Department of Anesthesiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Yizhi Pan
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Yi Luo
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Zhen Liu
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Jiankai Huang
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
,
Qi Wu
1   Department of Cardiology, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
› Author Affiliations

Abstract

Exercise training (ET) could improve myocardial infarction (MI), and microRNA-497 is highly associated with MI. This study aimed to investigate whether the regulation of miR-497 is involved in the positive effects of ET on MI. MI rat models induced by left anterior descending (LAD) were subjected to interval training and infarct size was observed. Blood and myocardial samples were collected from the rats for determining the expressions of miR-497. To evaluate the functions of miR-497, miR-497 agomir and antagomir were injected accordingly into grouped rats during ET, and subsequently, the expressions of apoptotic and inflammatory factors were determined. ET reduced the infarct size in MI rats and inhibited the levels of miR-497. MiR-497 agomir injection enlarged the infarct size, and reversed the shrunk infarct size induced by ET. However, miR-497 antagomir further promoted the positive effect on MI improved by ET. Chloride voltage-gated channel 3 (CLCN3) was identified as the most possible target for miR-497. Moreover, ET improving MI also involved the regulation of apoptotic and inflammatory factors. The mechanisms underlying the positive effects of ET on MI were highly associated with the regulation of miR-497.



Publication History

Received: 00 00 2019

Accepted: 16 September 2019

Article published online:
11 March 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Moraes-Silva IC, Rodrigues B, Coelho-Junior HJ. et al Myocardial infarction and exercise training: Evidence from basic science. Adv Exp Med Biol 2017; 999: 139-153
  • 2 Santos-Gallego CG, Picatoste B, Badimon JJ. Pathophysiology of acute coronary syndrome. Curr Atheroscler Rep 2014; 16: 401
  • 3 Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 2000; 35: 569-582
  • 4 Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000; 101: 2981-2988
  • 5 McKay RG, Pfeffer MA, Pasternak RC. et al Left ventricular remodeling after myocardial infarction: A corollary to infarct expansion. Circulation 1986; 74: 693-702
  • 6 Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling: Mechanisms: Part 1 of 2. Circulation 2013; 128: 388-400
  • 7 Deng Y, Wu W, Guo S. et al Altered mTOR and Beclin-1 mediated autophagic activation during right ventricular remodeling in monocrotaline-induced pulmonary hypertension. Respir Res 2017; 18: 53
  • 8 Li J, Cai S, Peng J. et al Time dependent distribution of microRNA 144 after intravenous delivery. Microrna 2016; 5: 36-49
  • 9 Li J, Cai SX, He Q. et al Intravenous miR-144 reduces left ventricular remodeling after myocardial infarction. Basic Res Cardiol 2018; 113: 36
  • 10 Ezekowitz JA, Kaul P, Bakal JA. et al Declining in-hospital mortality and increasing heart failure incidence in elderly patients with first myocardial infarction. J Am Coll Cardiol 2009; 53: 13-20
  • 11 Mao S, Zhang X, Shao B. et al Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and rationale of a pragmatic randomized controlled trial. Cardiovasc Drugs Ther 2016; 30: 315-322
  • 12 Zhang YM, Lu Y, Tang Y. et al The effects of different initiation time of exercise training on left ventricular remodeling and cardiopulmonary rehabilitation in patients with left ventricular dysfunction after myocardial infarction. Disabil Rehabil 2016; 38: 268-276
  • 13 Maessen M, Eijsvogels T, Stevens G. et al enefits of lifelong exercise training on left ventricular function after myocardial infarction. Eur J Prev Cardiol 2017; 24: 1856-1866
  • 14 Haykowsky M, Scott J, Esch B. et al A meta-analysis of the effects of exercise training on left ventricular remodeling following myocardial infarction: start early and go longer for greatest exercise benefits on remodeling. Trials 2011; 12: 92
  • 15 Mc GG, Gaze D, Oxborough D. et al Reverse left ventricular remodeling: effect of cardiac rehabilitation exercise training in myocardial infarction patients with preserved ejection fraction. Eur J Phys Rehabil Med 2016; 52: 370-378
  • 16 Puhl SL, Muller A, Wagner M. et al Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice. Am J Physiol Heart Circ Physiol 2015; 309: H345-H359
  • 17 Batkai S, Bar C, Thum T. MicroRNAs in right ventricular remodelling. Cardiovasc Res 2017; 113: 1433-1440
  • 18 Montgomery RL, Hullinger TG, Semus HM. et al Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation 2011; 124: 1537-1547
  • 19 Feng L, Zhu Y, Zhang Y. et al LncRNA GACAT3 promotes gastric cancer progression by negatively regulating miR-497 expression. Biomed Pharmacother 2018; 97: 136-142
  • 20 Furuta M, Kozaki K, Tanimoto K. et al The tumor-suppressive miR-497-195 cluster targets multiple cell-cycle regulators in hepatocellular carcinoma. PLoS One 2013; 8: e60155
  • 21 Guo D, Wang Y, Ren K. et al Knockdown of LncRNA PVT1 inhibits tumorigenesis in non-small-cell lung cancer by regulating miR-497 expression. Exp Cell Res 2018; 362: 172-179
  • 22 Li Z, Lu J, Luo Y. et al High association between human circulating microRNA-497 and acute myocardial infarction. ScientificWorld Journal 2014; 2014: 931845
  • 23 Li X, Zeng Z, Li Q. et al Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy. Oncotarget 2015; 6: 18829-18844
  • 24 Tang Y, Zhong Z, Wang X. et al microRNA-497 inhibition mitigates myocardial infarction via enhancing wingless/integrated signal pathway in bone marrow mesenchymal stem cells. J Cell Biochem 2019; 120: 13403-13412
  • 25 Harriss D, MacSween A, Atkinson G. Standards for ethics in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
  • 26 Rolim N, Skardal K, Hoydal M. et al Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction. Basic Res Cardiol 2015; 110: 44
  • 27 Fleige S, Walf V, Huch S. et al Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR. Biotechnol Lett 2006; 28: 1601-1613
  • 28 Kraus WE, Bittner V, Appel L. et al The National Physical Activity Plan: A call to action from the American Heart Association: A science advisory from the American Heart Association. Circulation 2015; 131: 1932-1940
  • 29 Yin KJ, Deng Z, Huang H. et al miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis 2010; 38: 17-26
  • 30 Ooi JY, Bernardo BC, McMullen JR. The therapeutic potential of miRNAs regulated in settings of physiological cardiac hypertrophy. Future Med Chem 2014; 6: 205-222
  • 31 Souza RW, Fernandez GJ, Cunha JP. et al Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure. Am J Physiol Heart Circ Physiol 2015; 309: H1629-H1641
  • 32 Shi J, Bei Y, Kong X. et al miR-17-3p Contributes to exercise-induced cardiac growth and protects against myocardial ischemia-reperfusion injury. Theranostics 2017; 7: 664-676
  • 33 Xiao L, He H, Ma L. et al Effects of miR-29a and miR-101a Expression on myocardial interstitial collagen generation after aerobic exercise in myocardial-infarcted rats. Arch Med Res 2017; 48: 27-34
  • 34 Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res 2002; 53: 31-47
  • 35 Nishikido T, Oyama J, Shiraki A. et al Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L attenuates the inflammatory response and infarct size in acute myocardial infarction. J Am Heart Assoc 2016; 5: e002863
  • 36 Vanhoutte D, Schellings M, Pinto Y. et al Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window. Cardiovasc Res 2006; 69: 604-613
  • 37 Creemers EE, Cleutjens JP, Smits JF. et al Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure?. Circ Res 2001; 89: 201-210
  • 38 Bozeat ND, Xiang SY, Ye LL. et al Activation of volume regulated chloride channels protects myocardium from ischemia/reperfusion damage in second-window ischemic preconditioning. Cell Physiol Biochem 2011; 28: 1265-1278
  • 39 Yamazaki J, Duan D, Janiak R. et al Functional and molecular expression of volume-regulated chloride channels in canine vascular smooth muscle cells. J Physiol 1998; 507: 729-736
  • 40 Diaz RJ, Armstrong SC, Batthish M. et al Enhanced cell volume regulation: a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes. J Mol Cell Cardiol 2003; 35: 45-58
  • 41 Yu Y, Ye L, Li YG. et al Heart-specific overexpression of the human short CLC-3 chloride channel isoform limits myocardial ischemia-induced ERP and QT prolongation. Int J Cardiol 2016; 214: 218-224
  • 42 Xiong D, Heyman NS, Airey J. et al Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice. J Mol Cell Cardiol 2010; 48: 211-219