Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs

Abstract

Fernandes T, Baraúna VG, Negrão CE, Phillips MI, Oliveira EM. Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs. Am J Physiol Heart Circ Physiol 309: H543-H552, 2015. First published June 12, 2015 doi:10.1152/ajpheart.00899.2014 hypertrophy is an important physiological compensatory mechanism in response to chronic increase in hemodynamic overload. There are two different forms of LV hypertrophy, one physiological and another pathological. Aerobic exercise induces beneficial physiological LV remodeling. The molecular/cellular mechanisms for this effect are not totally known, and here we review various mechanisms including the role of microRNA (miRNA). Studies in the heart, have identified antihypertrophic . Four miRNAs are recognized as cardiacspecific: miRNA-1, -133a/b, -208a/b, and -499 and called myomiRs. In our studies we have shown that miRNAs respond to swimming aerobic exercise by 1) decreasing cardiac fibrosis through miRNA-29 increasing and inhibiting collagen, 2) increasing angiogenesis through miRNA-126 by inhibiting negative regulators of the VEGF pathway, and 3) modulating the renin-angiotensin system through the miRNAs-27a/b and -143. Exercise training also increases cardiomyocyte growth and survival by swimming-regulated miRNA-1, -21, -27a/b, -29a/c, -30e, -99b, -100, -124, -126, -133a/b, -143, -144, -145, -208a, and -222 and running-regulated miRNA-1, -26, -27a, -133, -143, -150, and -222, which influence genes associated with the heart remodeling and angiogenesis. We conclude that there is a potential role of these miRNAs in promoting cardioprotective effects on physiological growth. cardiac hypertrophy; angiogenesis; swimming training; running training; microRNA THIS ARTICLE is part of a collection on Exercise Training in Cardiovascular Disease: Cell, Molecular, and Integrative Perspectives. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.EXERCISE TRAINING IS the most effective nonpharmacological intervention to reduce cardiovascular disease (CVD). Its prescription is recommended by the guidelines of the most important entities, such as the American College of Sport Medicine and the American Heart Association (39).Exercise training is well known to promote beneficial adaptations in the cardiovascular system which can vary according to type, intensity, and duration of exercise (32). Exercise training induces marked beneficial systemic effects on metabolism control, skeletal muscle, cognitive function, and cardiovascular function (30, 39). Among them, the set of adaptations induced in the myocardium are collectively referred to as "athlete's heart" and includes increased cardiac mass, formations of new blood vessels, and decreased collagen content (15a, 17, 20, 23, 77, 91). Individuals with high levels of physical activity have a lower prevalence and lower death rates from CVD (32, 86). Thus exercise training has been established not only as a way to ma...

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Interestingly, recent discoveries showed that circulating miR‐214 was up‐regulated in the early phase after AMI but then gradually decreased to near normal levels 163. Aerobic exercise training can alter the cardiac miRNA expression in physiological cardiac remodelling, such as miR‐1, miR‐150, miR‐21, miR‐122, miR‐126 and miR‐208 164. Mechanically, miR‐1 is enriched in cardiomyocytes and modulates myogenesis, cardiac development and hypertrophy, and miR‐208 is a cardiac‐specific miRNA expressed by introns of myosin heavy chains and involved in stress‐dependent cardiac growth and gene expression 165.…”

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

“…miR-1, miR-133, miR199a/b, miR-21, miR-23, miR-26, miR-29, miR-9, miR-98, and miR-499) have been shown to exert either a positive or negative influence on pathological cardiac hypertrophy (4 -6). Whereas several studies have recently profiled microRNA expression signatures in rat physiological hypertrophic hearts induced by swimming or treadmill training, it still remains unknown how dys-regulated miRNAs contribute to physiological hypertrophy (7)(8)(9)(10).…”

MicroRNAs in health and disease

“…37 A study demonstrated the beneficial effects of aerobic exercise training on cardiac remodeling through its effect on certain miRNAs. 38 The effects included decreasing cardiac fibrosis by inhibiting collagen through upregulation of miR-29, inhibition of negative regulators of VEGF pathway. These effects of miR-126 in turn increase angiogenesis and modulation of the renin-angiotensin system by miRNAs-27a/ b and -143.…”

“…These effects of miR-126 in turn increase angiogenesis and modulation of the renin-angiotensin system by miRNAs-27a/ b and -143. 38 …”