Circulating microRNAs fluctuations in exercise-induced cardiac remodeling: A systematic review

  1. Vallecillo Hernández, Néstor 2
  2. Fabian Sanchis-Gomar 2
  3. Miriam Arnau-Moyano 2
  4. Lidia Daimiel 3
  5. Giuseppe Lippi 7
  6. Roman Leischik 4
  7. Thomas Yvert 2
  8. Sergio L Jiménez 5
  9. Catalina Santiago 2
  10. Helios Pareja-Galeano 6
  1. 1 Universitat de València
    info

    Universitat de València

    Valencia, España

    ROR https://ror.org/043nxc105

  2. 2 Universidad Europea de Madrid
    info

    Universidad Europea de Madrid

    Madrid, España

    ROR https://ror.org/04dp46240

  3. 3 Instituto IMDEA Alimentación
    info

    Instituto IMDEA Alimentación

    Madrid, España

    ROR https://ror.org/04g4ezh90

  4. 4 Witten/Herdecke University
    info

    Witten/Herdecke University

    Witten, Alemania

    ROR https://ror.org/00yq55g44

  5. 5 Universidad Rey Juan Carlos
    info

    Universidad Rey Juan Carlos

    Madrid, España

    ROR https://ror.org/01v5cv687

  6. 6 Universidad Autónoma de Madrid
    info

    Universidad Autónoma de Madrid

    Madrid, España

    ROR https://ror.org/01cby8j38

  7. 7 University of Verona
    info

    University of Verona

    Verona, Italia

    ROR https://ror.org/039bp8j42

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Revista:
American Journal of Translational Research

ISSN: 1943-8141

Año de publicación: 2021

Volumen: 13

Número: 12

Páginas: 13298-13309

Tipo: Artículo

PMID: 35035676 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: American Journal of Translational Research

Resumen

MicroRNAs (miRNAs) are small non-coding RNAs that participate in gene expression regulation. It has been observed that circulating levels of miRNAs may fluctuate during exercise, showing numerous cardiac biological and physiological effects such as structural and functional adaptations. We aimed to provide an overview of the currently available information concerning the role of circulating miRNAs in cardiovascular adaptations in response to acute and/or chronic exercise training. Relevant studies published were searched in three databases: PubMed, Web of Science and Scopus. A combination of the following keywords was used: (“microRNA” OR “miRNA” OR “miR” AND “exercise” OR “training” OR “physical activity”) AND “(heart hypertrophy” OR “cardiac remodeling” OR “cardiac muscle mass” OR “cardiac hypertrophy”). Only experimental studies, written in English and conducted in healthy individuals were included. Five articles met the inclusion criteria and were finally included in this systematic review after reviewing both title, abstract and full-text. A total of thirty-six circulating cardiac-related miRNAs were analyzed, but only five of them (miR-1, miR-133a, miR-146a, miR-206 and miR-221) were directly associated with cardiac adaptations parameters, while two of them (miR-1 and miR-133a) were related to cardiac hypertrophy. Most of them were upregulated immediately after a marathon and returned to basal levels at longer times. Therefore, we conclude that, although evidence is still limited, and long-term studies are needed to obtain more robust evidence, exercise is more likely to affect circulating cardiac-related miRNAs levels.

Referencias bibliográficas

  • Huh JY, Mougios V, Kabasakalis A, Fatouros I, Siopi A, Douroudos II, Filippaios A, Panagiotou G, Park KH and Mantzoros CS. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. J Clin Endocrinol Metab 2014; 99: E2154-2161.
  • [2] Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD and Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007; 39: 1423-1434.
  • [3] Fagard R. Athlete’s heart. Heart 2003; 89: 1455-1461.
  • [4] Golbidi S and Laher I. Exercise and the cardiovascular system. Cardiol Res Pract 2012; 2012: 210852.
  • Pluim BM, Zwinderman AH, van der Laarse A and van der Wall EE. The athlete’s heart. A meta-analysis of cardiac structure and function. Circulation 2000; 101: 336-344.
  • [6] Wei X, Liu X and Rosenzweig A. What do we know about the cardiac benefits of exercise? Trends Cardiovasc Med 2015; 25: 529-536.
  • [7] Lenk K, Erbs S, Hollriegel R, Beck E, Linke A, Gielen S, Winkler SM, Sandri M, Hambrecht R, Schuler G and Adams V. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Prev Cardiol 2012; 19: 404-411.
  • [8] McMullen JR, Amirahmadi F, Woodcock EA, Schinke-Braun M, Bouwman RD, Hewitt KA, Mollica JP, Zhang L, Zhang Y, Shioi T, Buerger A, Izumo S, Jay PY and Jennings GL. Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A 2007; 104: 612-617.
  • [9] Quindry J, French J, Hamilton K, Lee Y, Mehta JL and Powers S. Exercise training provides cardioprotection against ischemia-reperfusion induced apoptosis in young and old animals. Exp Gerontol 2005; 40: 416-425.
  • [10] Schuttler D, Clauss S, Weckbach LT and Brunner S. Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells 2019; 8: 1128.
  • [11] Tian J, An X and Niu L. Role of microRNAs in cardiac development and disease. Exp Ther Med 2017; 13: 3-8.
  • [12] Zhou SS, Jin JP, Wang JQ, Zhang ZG, Freedman JH, Zheng Y and Cai L. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin 2018; 39: 1073-1084.
  • [13] Catalanotto C, Cogoni C and Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci 2016; 17: 1712.
  • [14] Zampetaki A, Willeit P, Drozdov I, Kiechl S and Mayr M. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res 2012; 93: 555-562.
  • [15] Sohel M. Extracellular/circulating microRNAs: release mechanisms, functions and challenges. Achiev Life Sci 2016; 10: 175-186.
  • [16] Fernandes T, Barauna VG, Negrao CE, Phillips MI and Oliveira EM. Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs. Am J Physiol Heart Circ Physiol 2015; 309: H543-552.
  • [17] Masi LN, Serdan TD, Levada-Pires AC, Hatanaka E, Silveira LD, Cury-Boaventura MF, PithonCuri TC, Curi R, Gorjao R and Hirabara SM. Regulation of gene expression by exercise-related microRNAs. Cell Physiol Biochem 2016; 39: 2381-2397
  • [18] Chen Y, Wakili R, Xiao J, Wu CT, Luo X, Clauss S, Dawson K, Qi X, Naud P, Shi YF, Tardif JC, Kaab S, Dobrev D and Nattel S. Detailed characterization of microRNA changes in a canine heart failure model: relationship to arrhythmogenic structural remodeling. J Mol Cell Cardiol 2014; 77: 113-124.
  • [19] Clauss S, Sinner MF, Kaab S and Wakili R. The role of micrornas in antiarrhythmic therapy for atrial fibrillation. Arrhythm Electrophysiol Rev 2015; 4: 146-155.
  • [20] Dawson K, Wakili R, Ordog B, Clauss S, Chen Y, Iwasaki Y, Voigt N, Qi XY, Sinner MF, Dobrev D, Kaab S and Nattel S. MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation. Circulation 2013; 127: 1466- 75, 1475e1-28.
  • [21] Ultimo S, Zauli G, Martelli AM, Vitale M, McCubrey JA, Capitani S and Neri LM. Cardiovascular disease-related miRNAs expression: potential role as biomarkers and effects of training exercise. Oncotarget 2018; 9: 17238-17254.
  • [22] Verdoorn KS, Matsuura C and Borges JP. Exercise for cardiac health and regeneration: killing two birds with one stone. Ann Transl Med 2017; 5: S13.
  • [23] Aengevaeren VL and Eijsvogels TMH. Coronary atherosclerosis in middle-aged athletes: current insights, burning questions, and future perspectives. Clin Cardiol 2020; 43: 863-871.
  • [24] Wang L, Lv Y, Li G and Xiao J. MicroRNAs in heart and circulation during physical exercise. J Sport Health Sci 2018; 7: 433-441.
  • [25] Moher D, Liberati A, Tetzlaff J and Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8: 336-341.
  • [26] de Gonzalo-Calvo D, Davalos A, FernandezSanjurjo M, Amado-Rodriguez L, Diaz-Coto S, Tomas-Zapico C, Montero A, Garcia-Gonzalez A, Llorente-Cortes V, Heras ME, Boraita Perez A, Diaz-Martinez AE, Ubeda N and IglesiasGutierrez E. Circulating microRNAs as emerging cardiac biomarkers responsive to acute exercise. Int J Cardiol 2018; 264: 130-136.
  • [27] Clauss S, Wakili R, Hildebrand B, Kaab S, Hoster E, Klier I, Martens E, Hanley A, Hanssen H, Halle M and Nickel T. MicroRNAs as biomarkers for acute atrial remodeling in marathon runners (The miRathon study--a sub-study of the Munich Marathon Study). PLoS One 2016; 11: e0148599.
  • [28] Baggish AL, Park J, Min PK, Isaacs S, Parker BA, Thompson PD, Troyanos C, D’Hemecourt P, Dyer S, Thiel M, Hale A and Chan SY. Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise. J Appl Physiol (1985) 2014; 116: 522-531.
  • [29] Mooren FC, Viereck J, Krüger K and Thum T. Circulating micrornas as potential biomarkers of aerobic exercise capacity. Am J Physiol Heart Circ Physiol 2014; 306: H557-63.
  • [30] Li Y, Yao M, Zhou Q, Cheng Y, Che L, Xu J, Xiao J, Shen Z and Bei Y. Dynamic regulation of circulating micrornas during acute exercise and long-term exercise training in basketball athletes. Front Physiol 2018; 9: 282.
  • [31] Sanna GD, Gabrielli E, De Vito E, Nusdeo G, Prisco D and Parodi G. Atrial fibrillation in athletes: from epidemiology to treatment in the novel oral anticoagulants era. J Cardiol 2018; 72: 269-276.
  • [32] Da Costa Martins PA and De Windt LJ. MicroRNAs in control of cardiac hypertrophy. Cardiovasc Res 2012; 93: 563-572.
  • [33] Besser J, Malan D, Wystub K, Bachmann A, Wietelmann A, Sasse P, Fleischmann BK, Braun T and Boettger T. MiRNA-1/133a clusters regulate adrenergic control of cardiac repolarization. PLoS One 2014; 9: e113449.
  • [34] Carè 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 and Condorelli G. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13: 613- 618.
  • [35] Soci UP, Fernandes T, Hashimoto NY, Mota GF, Amadeu MA, Rosa KT, Irigoyen MC, Phillips MI and Oliveira EM. MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. Physiol Genomics 2011; 43: 665-673.
  • [36] Drummond MJ, McCarthy JJ, Fry CS, Esser KA and Rasmussen BB. Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am J Physiol Endocrinol Metab 2008; 295: E1333- 1340.
  • [37] Rivas DA, Lessard SJ, Rice NP, Lustgarten MS, So K, Goodyear LJ, Parnell LD and Fielding RA. Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. FASEB J 2014; 28: 4133-4147.
  • [38] Nielsen S, Scheele C, Yfanti C, Akerstrom T, Nielsen AR, Pedersen BK and Laye MJ. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol 2010; 588: 4029-4037.
  • [39] Russell AP, Lamon S, Boon H, Wada S, Guller I, Brown EL, Chibalin AV, Zierath JR, Snow RJ, Stepto N, Wadley GD and Akimoto T. Regulation of miRNAs in human skeletal muscle following acute endurance exercise and shortterm endurance training. J Physiol 2013; 591: 4637-4653.
  • [40] Siracusa J, Koulmann N and Banzet S. Circulating myomiRs: a new class of biomarkers to monitor skeletal muscle in physiology and medicine. J Cachexia Sarcopenia Muscle 2018; 9: 20-27.
  • [41] Guescini M, Canonico B, Lucertini F, Maggio S, Annibalini G, Barbieri E, Luchetti F, Papa S and Stocchi V. Muscle releases alpha-sarcoglycan positive extracellular vesicles carrying miRNAs in the bloodstream. PLoS One 2015; 10: e0125094.
  • [42] Xiao L, He H, Ma L, Da M, Cheng S, Duan Y, Wang Q, Wu H, Song X, Duan W, Tian Z and Hou Y. 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.
  • [43] Roncarati R, Viviani Anselmi C, Losi MA, Papa L, Cavarretta E, Da Costa Martins P, Contaldi C, Saccani Jotti G, Franzone A, Galastri L, Latronico MV, Imbriaco M, Esposito G, De Windt L, Betocchi S and Condorelli G. Circulating miR29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2014; 63: 920-927.
  • [44] Davidsen PK, Gallagher IJ, Hartman JW, Tarnopolsky MA, Dela F, Helge JW, Timmons JA and Phillips SM. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J Appl Physiol (1985) 2011; 110: 309- 317.
  • [45] Hakansson KEJ, Sollie O, Simons KH, Quax PHA, Jensen J and Nossent AY. Circulating small non-coding RNAs as biomarkers for recovery after exhaustive or repetitive exercise. Front Physiol 2018; 9: 1136.
  • [46] Massart J, Sjogren RJO, Lundell LS, Mudry JM, Franck N, O’Gorman DJ, Egan B, Zierath JR and Krook A. Altered miR-29 expression in type 2 diabetes influences glucose and lipid metabolism in skeletal muscle. Diabetes 2017; 66: 1807-1818.
  • [47] Ma Z, Qi J, Meng S, Wen B and Zhang J. 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.
  • [48] Palabiyik O, Tastekin E, Doganlar ZB, Tayfur P, Dogan A and Vardar SA. Alteration in cardiac PI3K/Akt/mTOR and ERK signaling pathways with the use of growth hormone and swimming, and the roles of miR21 and miR133. Biomed Rep 2019; 0: 1-10.
  • [49] Wahl P, Wehmeier UF, Jansen FJ, Kilian Y, Bloch W, Werner N, Mester J and Hilberg T. Acute ef fects of different exercise protocols on the circulating vascular microRNAs -16, -21, and -126 in trained subjects. Front Physiol 2016; 7: 643.
  • [50] Nielsen S, Akerstrom T, Rinnov A, Yfanti C, Scheele C, Pedersen BK and Laye MJ. The miRNA plasma signature in response to acute aerobic exercise and endurance training. PLoS One 2014; 9: e87308.
  • [51] Xu T, Zhou Q, Che L, Das S, Wang L, Jiang J, Li G, Xu J, Yao J, Wang H, Dai Y and Xiao J. Circulating miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in chronic heart failure patients. Oncotarget 2016; 7: 12414-12425.
  • [52] Sheedy FJ. Turning 21: induction of miR-21 as a key switch in the inflammatory response. Front Immunol 2015; 6: 19.
  • [53] Njock MS, Cheng HS, Dang LT, Nazari-Jahantigh M, Lau AC, Boudreau E, Roufaiel M, Cybulsky MI, Schober A and Fish JE. Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing antiinflammatory microRNAs. Blood 2015; 125: 3202-3212.
  • [54] Canfran-Duque A, Rotllan N, Zhang X, Fernandez-Fuertes M, Ramirez-Hidalgo C, Araldi E, Daimiel L, Busto R, Fernandez-Hernando C and Suarez Y. Macrophage deficiency of miR21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Mol Med 2017; 9: 1244-1262.
  • [55] Fernandes T, Hashimoto NY, Magalhaes FC, Fernandes FB, Casarini DE, Carmona AK, Krieger JE, Phillips MI and Oliveira EM. Aerobic exercise training-induced left ventricular hypertrophy involves regulatory microRNAs, decreased angiotensin-converting enzyme-angiotensin II, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1- 7). Hypertension 2011; 58: 182-189.
  • [56] Zhang T, Brinkley TE, Liu K, Feng X, Marsh AP, Kritchevsky S, Zhou X and Nicklas BJ. Circulating miRNAs as biomarkers of gait speed responses to aerobic exercise training in obese older adults. Aging (Albany NY) 2017; 9: 900- 913.
  • [57] Domanska-Senderowska D, Laguette MN, Jegier A, Cieszczyk P, September AV and Brzezianska-Lasota E. MicroRNA profile and adaptive response to exercise training: a review. Int J Sports Med 2019; 40: 227-235.
  • [58] Arad M, Seidman CE and Seidman JG. AMPactivated protein kinase in the heart: role during health and disease. Circ Res 2007; 100: 474-488.
  • [59] Chen C, Ponnusamy M, Liu C, Gao J, Wang K and Li P. MicroRNA as a therapeutic target in cardiac remodeling. Biomed Res Int 2017; 2017: 1278436.
  • [60] Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo MA, Cimino V, De Marinis L, Frustaci A, Catalucci D and 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 2009; 120: 2377-2385.
  • [61] Shi JY, Chen C, Xu X and Lu Q. miR-29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy. Acta Physiol (Oxf) 2019; 227: e13323.
  • [62] Sayed D, Hong C, Chen IY, Lypowy J and Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 2007; 100: 416-424.