Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway

Ma, Zhichao; Qi, Jie; Meng, Shuai; Wen, Baoju; Zhang, Jun

doi:10.1007/s00421-013-2685-9

Cited by 90 publications

(78 citation statements)

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“…miRNAs are considered promising therapeutic targets for CVD (4,15,71,74,85,90). We have found numerous miRNAs that play specific roles in regulating gene expression by exercise training (15a, 20, 21, 24, 65, 91) and confirmed by Ma et al (58) and Martinelli et al (61). The aim of this review is provide an overview of exercise training effects on physiological cardiac remodeling and the involvement of miRNAs in this process.…”

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confidence: 52%

“…The predicted target genes of miRNA-26b and -150 may be involved in physiological cardiac hypertrophy induced by exercise training, since they are related to survival pathways, such as IGF-1/PI3K signaling and glycogen synthase kinase-3␤, respectively. Interestingly, Ma et al (58) identified miRNAs that target the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway in swimming training-induced cardiac hypertrophy. The authors observed that exercise training increased cardiac miRNA-21 and -144 expression associated with a reduction in their target gene phosphatase and tensin homolog (negative regulator of the PI3K/Akt/mTOR pathway).…”

Section: Mirnas Cardiac Hypertrophy and Exercise Trainingmentioning

confidence: 99%

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

Fernandes

Baraúna

Negräo

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

130

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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...

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confidence: 52%

Section: Mirnas Cardiac Hypertrophy and Exercise Trainingmentioning

confidence: 99%

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

Fernandes

Baraúna

Negräo

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

130

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“…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).…”

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confidence: 99%

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

Yang

Wang

et al. 2016

Journal of Biological Chemistry

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MicroRNAs (miRNAs) have been extensively examined in pathological cardiac hypertrophy. However, few studies focused on profiling the miRNA alterations in physiological hypertrophic hearts. In this study we generated a transgenic mouse model with cardiac-specific overexpression of miR-223. Our results showed that elevation of miR-223 caused physiological cardiac hypertrophy with enhanced cardiac function but no fibrosis. Using the next generation RNA sequencing, we observed that most of dys-regulated genes (e.g. Atf3/5, Egr1/3, Sfrp2, Itgb1, Ndrg4, Akip1, Postn, Rxfp1, and Egln3) in miR-223-transgenic hearts were associated with cell growth, but they were not directly targeted by miR-223. Interestingly, these dysregulated genes are known to regulate the Akt signaling pathway. We further identified that miR-223 directly interacted with 3-UTRs of FBXW7 and Acvr2a, two negative regulators of the Akt signaling. However, we also validated that miR-223 directly inhibited the expression of IGF-1R and ␤1-integrin, two positive regulators of the Akt signaling. Lastly, Western blotting did reveal that Akt was activated in miR-223-overexpressing hearts. Adenovirus-mediated overexpression of miR-223 in neonatal rat cardiomyocytes induced cell hypertrophy, which was blocked by the addition of MK2206, a specific inhibitor of Akt. Taken together, these data represent the first piece of work showing that miR-223 tips the balance of promotion and inactivation of Akt signaling cascades toward activation of Akt, a key regulator of physiological cardiac hypertrophy. Thus, our study suggests that the ultimate phenotype outcome of a miRNA may be decided by the secondary net effects of the whole target network rather than by several primary direct targets in an organ/tissue.Cardiac hypertrophy is an adaptive mechanism of cardiomyocytes to different forms of injury or stress, such as myocardial infarction, hypertension, and valve disease (pathological) or chronic exercise training (physiological) (1). Both pathological and physiological cardiac hypertrophy types are featured with increased myocyte size, but they have distinct molecular and functional phenotypes (2). Pathological cardiac hypertrophy is often associated with interstitial fibrosis and increased myocyte necrosis/apoptosis, leading to cardiac dysfunction (1, 2). By contrast, exercise training-induced physiological cardiac hypertrophy is characterized by overall normal cardiac structure and function, presenting an adaptive beneficial response (1, 2). Indeed, exercise training is clinically recommended as the most effective non-pharmacological intervention to reduce cardiovascular disease (2). Thus, elucidating the molecular mechanisms underlying physiological cardiac hypertrophy would help us identify novel therapies for the treatment of cardiovascular disease.MicroRNAs (miRNAs) 3 are small, endogenous, non-coding RNAs of ϳ22 to 26 nucleotides in length that function primarily as post-transcriptional regulators (3). Importantly, a single miRNA does not only regulate one gene ...

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“…The calcineurin-nuclear factor of activated T-cells and phosphoinositide 3-kinase (PI-3K), Akt, glycogen synthase kinase 3 (GSK-3) are among the major signaling molecules governing the cardiac hypertrophy response [12]. The results of in vivo and in vitro experiments indicate that insulin-like growth factor (IGF)-1 is an important growth factor which, by its receptors, mediates cardiac growth in a PI-3K dependent manner [12,13]. However, the precise role of IGF-1 in the regulation of cardiac structure under both physiological stress and the direct effect of testosterone remains debatable [14,15,16].…”

Section: Experimental Animals and Hormonal Treatmentmentioning

confidence: 99%

Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

Żebrowska¹,

Sadowska-Krępa²,

Jagsz³

et al. 2017

Open Life Sciences

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Abstract:Objective: Several studies have suggested that testosterone exerts a growth-promoting effect in the heart. Limited data are available regarding interactions between possible endocrine/paracrine effects in response to exercise training. Therefore, we examined supraphysiological testosterone-induced heart hypertrophy and cardiac insulin-like growth factor (IGF)-1 content in sedentary and exercise-trained rats. Design: Male Wistar rats (n=33) were randomly allocated to groups with a 6-week endurance training with or without testosterone, and sedentary animals with or without testosterone. The hormone (20 mg/250 g body weight was administrated once a week for six weeks. After six weeks the animals were anesthetized, euthanized and the heart was excised and weighed. The left ventricle was separated for biochemical analyses. Results: Testosterone-treated animals showed significantly higher cardiac IGF-1 content compared to untreated control and trained groups (p=0.01). The administration of supraphysiological testosterone significantly increased the heart weight to body weight ratio (HW/BW, p<0.01). A significant positive correlation was seen between IGF-1 levels and the HW/BW ratio (p=0.002; r=0.50) and between serum total testosterone levels and HW/BW (p=0.000; r=0.79). Conclusions:The results demonstrate that increased

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Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway

Abstract: These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, changing the expression of specific miRNAs targeting the PIK3/AKT/mTOR signaling pathway and its negative regulators.

Cited by 90 publications

References 81 publications

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

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

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

Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

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