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CC BY-NC-ND 4.0 · Int J Sports Med 2022; 43(03): 219-229
DOI: 10.1055/a-1539-6702
Physiology & Biochemistry

Excessive Treadmill Training Produces different Cardiac-related MicroRNA Profiles in the Left and Right Ventricles in Mice

Jing Yang‡
1   The Research Center of Military Exercise Science, The Army Engineering University of PLA, Nanjing, China
,
Lin Xu‡
1   The Research Center of Military Exercise Science, The Army Engineering University of PLA, Nanjing, China
2   Department of Exercise and Heath, Nanjing Sport Institute, Nanjing, China
3   State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
,
Xin Yin
2   Department of Exercise and Heath, Nanjing Sport Institute, Nanjing, China
3   State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
,
Yi Li Zheng
3   State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
,
Hai Peng Zhang
2   Department of Exercise and Heath, Nanjing Sport Institute, Nanjing, China
3   State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
,
Sheng Jia Xu
1   The Research Center of Military Exercise Science, The Army Engineering University of PLA, Nanjing, China
,
Wei Wang
1   The Research Center of Military Exercise Science, The Army Engineering University of PLA, Nanjing, China
,
Sen Wang
4   Department of Geriatric Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
Chen Yu Zhang
3   State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
,
Ji Zheng Ma
1   The Research Center of Military Exercise Science, The Army Engineering University of PLA, Nanjing, China
› Author Affiliations Funding: The authors acknowledge that this work was supported by the Research Special Fund for PLA University of Science and Technology (KYJYZLXY1603–9, 40). The Research Innovation Program for College Graduates of Jiangsu Province (KYCX19_1471). The Research Fund for Postgraduate in Military (KYJXJQJY2001). The Natural Science Foundation of Jiangsu Province (2021).
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Abstract

High-volume training followed by inadequate recovery may cause overtraining. This process may undermine the protective effect of regular exercise on the cardiovascular system and may increase the risk of pathological cardiac remodelling. We evaluated whether chronic overtraining changes cardiac-related microRNA profiles in the left and right ventricles. C57BL/6 mice were divided into the control, normal training, and overtrained by running without inclination, uphill running or downhill running groups. After an 8-week treadmill training protocol, the incremental load test and training volume results showed that the model had been successfully established. The qRT-PCR results showed increased cardiac miR-1, miR-133a, miR-133b, miR-206, miR-208b and miR-499 levels in the left ventricle of the downhill running group compared with the left ventricle of the control group. Similarly, compared with the control group, the downhill running induced increased expression of miR-21, miR-17–3p, and miR-29b in the left ventricle. Unlike the changes in the left ventricle, no difference in the expression of the tested miRNAs was observed in the right ventricle. Briefly, our results indicated that overtraining generally affects key miRNAs in the left ventricle (rather than the right ventricle) and that changes in individual miRNAs may cause either adaptive or maladaptive remodelling with overtraining.

Key words

excessive training - aerobic training - myocardial - microRNAs

Supplementary Material



Publication History

Received: 02 July 2020

Accepted: 17 June 2021

Article published online:
20 August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Hawley JA, Hargreaves M, Joyner MJ. et al. Integrative biology of exercise. Cell 2014; 159: 738-749 doi:10.1016/j.cell.2014.10.029
    CrossrefPubMedSearch in Google Scholar
  • 2 Seo DY, Kwak HB, Kim AH. et al. Cardiac adaptation to exercise training in health and disease. Pflugers Arch 2020; 472: 155-168 doi:10.1007/s00424-019-02266-3
    CrossrefPubMedSearch in Google Scholar
  • 3 Bernardo BC, Ooi JYY, Weeks KL. et al. Understanding key mechanisms of exercise-induced cardiac protection to mitigate disease: current knowledge and emerging concepts. Physiol Rev 2018; 98: 419-475 doi:10.1152/physrev.00043.2016
    CrossrefPubMedSearch in Google Scholar
  • 4 Wilson MG, Ellison GM, Cable NT. Basic science behind the cardiovascular benefits of exercise. Br J Sports Med 2016; 50: 93-99 doi:10.1136/bjsports-2014-306596rep
    CrossrefPubMedSearch in Google Scholar
  • 5 Morganroth J, Maron BJ, Henry WL. et al. Comparative left ventricular dimensions in trained athletes. Ann Intern Med 1975; 82: 521-524 doi:10.7326/0003-4819-82-4-521
    CrossrefPubMedSearch in Google Scholar
  • 6 Ellison GM, Waring CD, Vicinanza C. et al. Physiological cardiac remodelling in response to endurance exercise training: Cellular and molecular mechanisms. Heart 2012; 98: 5-10 doi:10.1136/heartjnl-2011-300639
    CrossrefPubMedSearch in Google Scholar
  • 7 Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 2018; 15: 387-407 doi:10.1038/s41569-018-0007-y
    CrossrefPubMedSearch in Google Scholar
  • 8 Fry AC, Kraemer WJ. Resistance exercise overtraining and overreaching. Neuroendocrine responses. Sports Med 1997; 23: 106-129 doi:10.2165/00007256-199723020-00004
    PubMedSearch in Google Scholar
  • 9 Meeusen R, Duclos M, Foster C. et al. Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Med Sci Sports Exerc 2013; 45: 186-205 doi:10.1249/MSS.0b013e318279a10a
    CrossrefPubMedSearch in Google Scholar
  • 10 da Rocha AL, Teixeira GR, Pinto AP. et al. Excessive training induces molecular signs of pathologic cardiac hypertrophy. J Cell Physiol 2018; 233: 8850-8861 doi:10.1002/jcp.26799
    CrossrefPubMedSearch in Google Scholar
  • 11 Fernandes T, Soci UP, Oliveira EM. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants. Braz J Med Biol Res 2011; 44: 836-847 doi:10.1590/s0100-879x2011007500112
    CrossrefPubMedSearch in Google Scholar
  • 12 Fernandes T, Barauna VG, Negrao CE. et al. Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs. Am J Physiol Heart Circ Physiol 2015; 309: H543-H552 doi:10.1152/ajpheart.00899.2014
    CrossrefPubMedSearch in Google Scholar
  • 13 Schuttler D, Clauss S, Weckbach LT. et al. Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells 2019; 8: 1128 doi:10.3390/cells8101128
    CrossrefPubMedSearch in Google Scholar
  • 14 Chistiakov DA, Orekhov AN, Bobryshev YV. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction). J Mol Cell Cardiol 2016; 94: 107-121 doi:10.1016/j.yjmcc.2016.03.015
    CrossrefPubMedSearch in Google Scholar
  • 15 Lindman BR, Dweck MR, Lancellotti P. et al. Management of asymptomatic severe aortic stenosis: Evolving Concepts in timing of valve replacement. JACC Cardiovasc Imaging 2020; 13: 481-493 doi:10.1016/j.jcmg.2019.01.036
    CrossrefPubMedSearch in Google Scholar
  • 16 Rodrigues JC, Amadu AM, Dastidar AG. et al. Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes. Heart 2016; 102: 1671-1679 doi:10.1136/heartjnl-2016-309576
    CrossrefPubMedSearch in Google Scholar
  • 17 Treibel TA, Lopez B, Gonzalez A. et al. Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients. Eur Heart J 2018; 39: 699-709 doi:10.1093/eurheartj/ehx353
    CrossrefPubMedSearch in Google Scholar
  • 18 Ravassa S, Lopez B, Querejeta R. et al. Phenotyping of myocardial fibrosis in hypertensive patients with heart failure. Influence on clinical outcome. J Hypertens 2017; 35: 853-861 doi:10.1097/HJH.0000000000001258
    CrossrefPubMedSearch in Google Scholar
  • 19 Carabello BA. Aortic stenosis: from pressure overload to heart failure. Heart Fail Clin 2006; 2: 435-442 doi:10.1016/j.hfc.2006.11.001
    CrossrefPubMedSearch in Google Scholar
  • 20 Batkai S, Bar C, Thum T. MicroRNAs in right ventricular remodelling. Cardiovasc Res 2017; 113: 1433-1440 doi:10.1093/cvr/cvx153
    CrossrefPubMedSearch in Google Scholar
  • 21 Pereira BC, Filho LA, Alves GF. et al. A new overtraining protocol for mice based on downhill running sessions. Clin Exp Pharmacol Physiol 2012; 39: 793-798 doi:10.1111/j.1440-1681.2012.05728.x
    CrossrefPubMedSearch in Google Scholar
  • 22 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817 doi:10.1055/a-1015-3123
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Kuipers H, Verstappen FT, Keizer HA. et al. Variability of aerobic performance in the laboratory and its physiologic correlates. Int J Sports Med 1985; 6: 197-201 doi:10.1055/s-2008-1025839
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Turgeman T, Hagai Y, Huebner K. et al. Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone. Neuromuscul Disord 2008; 18: 857-868 doi:10.1016/j.nmd.2008.06.386
    CrossrefPubMedSearch in Google Scholar
  • 25 Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9: 671-675 doi:10.1038/nmeth.2089
    CrossrefPubMedSearch in Google Scholar
  • 26 Vega RB, Konhilas JP, Kelly DP. et al. Molecular mechanisms underlying cardiac adaptation to exercise. Cell Metab 2017; 25: 1012-1026 doi:10.1016/j.cmet.2017.04.025
    CrossrefPubMedSearch in Google Scholar
  • 27 Wang L, Lv Y, Li G. et al. MicroRNAs in heart and circulation during physical exercise. J Sport Health Sci 2018; 7: 433-441 doi:10.1016/j.jshs.2018.09.008
    CrossrefPubMedSearch in Google Scholar
  • 28 Domanska-Senderowska D, Laguette MN, Jegier A. et al. MicroRNA profile and adaptive response to exercise training: a review. int j Sports Med 2019; 40: 227-235 doi:10.1055/a-0824-4813
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Soci UP, Fernandes T, Hashimoto NY. et al. MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. Physiol Genomics 2011; 43: 665-673 doi:10.1152/physiolgenomics.00145.2010
    CrossrefPubMedSearch in Google Scholar
  • 30 Ai J, Zhang R, Gao X. et al. Overexpression of microRNA-1 impairs cardiac contractile function by damaging sarcomere assembly. Cardiovasc Res 2012; 95: 385-393 doi:10.1093/cvr/cvs196
    CrossrefPubMedSearch in Google Scholar
  • 31 Zhang Y, Sun L, Zhang Y. et al. Overexpression of microRNA-1 causes atrioventricular block in rodents. Int J Biol Sci 2013; 9: 455-462 doi:10.7150/ijbs.4630
    CrossrefPubMedSearch in Google Scholar
  • 32 Kambis TN, Shahshahan HR, Kar S. et al. Transgenic expression of miR-133a in the diabetic akita heart prevents cardiac remodeling and cardiomyopathy. Front Cardiovasc Med 2019; 6: 45 doi:10.3389/fcvm.2019.00045
    CrossrefPubMedSearch in Google Scholar
  • 33 Sucharov C, Bristow MR, Port JD. miRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol 2008; 45: 185-192 doi:10.1016/j.yjmcc.2008.04.014
    CrossrefPubMedSearch in Google Scholar
  • 34 Hart EC, Charkoudian N, Wallin BG. et al. Sex and ageing differences in resting arterial pressure regulation: the role of the beta-adrenergic receptors. J Physiol 2011; 589: 5285-5297 doi:10.1113/jphysiol.2011.212753
    CrossrefPubMedSearch in Google Scholar
  • 35 Murphy E. Estrogen signaling and cardiovascular disease. Circ Res 2011; 109: 687-696 doi:10.1161/CIRCRESAHA.110.236687
    CrossrefPubMedSearch in Google Scholar
  • 36 Dworatzek E, Mahmoodzadeh S, Schubert C. et al. Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta. Cardiovasc Res 2014; 102: 418-428 doi:10.1093/cvr/cvu065
    CrossrefPubMedSearch in Google Scholar
  • 37 Schipper ME, van Kuik J, de Jonge N. et al. Changes in regulatory microRNA expression in myocardium of heart failure patients on left ventricular assist device support. J Heart Lung Transplant 2008; 27: 1282-1285 doi:10.1016/j.healun.2008.09.005
    CrossrefPubMedSearch in Google Scholar
  • 38 Yang Y, Del Re DP, Nakano N. et al. miR-206 mediates YAP-induced cardiac hypertrophy and survival. Circ Res 2015; 117: 891-904 doi:10.1161/CIRCRESAHA.115.306624
    CrossrefPubMedSearch in Google Scholar
  • 39 Yan Y, Dang H, Zhang X. et al. The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B. Biosci Rep 2020; 40: BSR20191000 doi:10.1042/BSR20191000
    CrossrefPubMedSearch in Google Scholar
  • 40 Soci UPR, Fernandes T, Barauna VG. et al. Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208. Clin Sci (Lond) 2016; 130: 2005-2015 doi:10.1042/CS20160480
    CrossrefPubMedSearch in Google Scholar
  • 41 Satoh M, Minami Y, Takahashi Y. et al. Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy. J Card Fail 2010; 16: 404-410 doi:10.1016/j.cardfail.2010.01.002
    CrossrefPubMedSearch in Google Scholar
  • 42 Gan Z, Rumsey J, Hazen BC. et al. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism. J Clin Invest 2013; 123: 2564-2575 doi:10.1172/JCI67652
    CrossrefPubMedSearch in Google Scholar
  • 43 Matkovich SJ, Hu Y, Eschenbacher WH. et al. Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy. Circ Res 2012; 111: 521-531 doi:10.1161/CIRCRESAHA.112.265736
    CrossrefPubMedSearch in Google Scholar
  • 44 Ma Z, Qi J, Meng S. et al. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol 2013; 113: 2473-2486 doi:10.1007/s00421-013-2685-9
    CrossrefPubMedSearch in Google Scholar
  • 45 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 doi:10.7150/thno.15162
    CrossrefPubMedSearch in Google Scholar
  • 46 Chaturvedi P, Kalani A, Medina I. et al. Cardiosome mediated regulation of MMP9 in diabetic heart: role of mir29b and mir455 in exercise. J Cell Mol Med 2015; 19: 2153-2161 doi:10.1111/jcmm.12589
    CrossrefPubMedSearch in Google Scholar
  • 47 Chivulescu M, Haugaa K, Lie OH. et al. Right ventricular remodeling in athletes and in arrhythmogenic cardiomyopathy. Scand Cardiovasc J 2018; 52: 13-19 doi:10.1080/14017431.2017.1416158
    CrossrefPubMedSearch in Google Scholar
  • 48 D'Andrea A, La Gerche A, Golia E. et al. Right heart structural and functional remodeling in athletes. Echocardiography 2015; 32: S11-S22 doi:10.1111/echo.12226
    CrossrefPubMedSearch in Google Scholar
  • 49 La Gerche A, Burns AT, Mooney DJ. et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 2012; 33: 998-1006 doi:10.1093/eurheartj/ehr397
    CrossrefPubMedSearch in Google Scholar
  • 50 Nogueira-Ferreira R, Ferreira R, Padrao AI. et al. One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats. J Physiol Biochem 2019; 75: 561-572 doi:10.1007/s13105-019-00705-4
    CrossrefPubMedSearch in Google Scholar
  • 51 Aoi W. Frontier impact of microRNAs in skeletal muscle research: a future perspective. Front Physiol 2014; 5: 495 doi:10.3389/fphys.2014.00495
    PubMedSearch in Google Scholar
  • 52 da Rocha AL, Pereira BC, Teixeira GR. et al. Treadmill slope modulates inflammation, fiber type composition, androgen, and glucocorticoid receptors in the skeletal muscle of overtrained mice. Front Immunol 2017; 8: 1378 doi:10.3389/fimmu.2017.01378
    CrossrefPubMedSearch in Google Scholar
  • 53 Davis JM, Murphy EA, Carmichael MD. et al. Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol 2007; 292: R2168-R2173 doi:10.1152/ajpregu.00858.2006
    CrossrefPubMedSearch in Google Scholar