scholarly journals JMJD1A Represses the Development of Cardiomyocyte Hypertrophy by Regulating the Expression of Catalase

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Rongjia Zang ◽  
Qingyun Tan ◽  
Fanrong Zeng ◽  
Dongwei Wang ◽  
Shuang Yu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Mechanism Study ◽  
Aortic Constriction ◽  
Rat Cardiomyocytes ◽  
Protein Levels

The histone demethylase JMJD family is involved in various physiological and pathological functions. However, the roles of JMJD1A in the cardiovascular system remain unknown. Here, we studied the function of JMJD1A in cardiac hypertrophy. The mRNA and protein levels of JMJD1A were significantly downregulated in the hearts of human patients with hypertrophic cardiomyopathy and the hearts of C57BL/6 mice underwent cardiac hypertrophy induced by transverse aortic constriction (TAC) surgery or isoproterenol (ISO) infusion. In neonatal rat cardiomyocytes (NRCMs), siRNA-mediated JMJD1A knockdown facilitated ISO or angiotensin II-induced increase in cardiomyocyte size, protein synthesis, and expression of hypertrophic fetal genes, including atrial natriuretic peptide (Anp), brain natriuretic peptide (Bnp), and Myh7. By contrast, overexpression of JMJD1A with adenovirus repressed the development of ISO-induced cardiomyocyte hypertrophy. We observed that JMJD1A reduced the production of total cellular and mitochondrial levels of reactive oxygen species (ROS), which was critically involved in the effects of JMJD1A because either N-acetylcysteine or MitoTEMPO treatment blocked the effects of JMJD1A deficiency on cardiomyocyte hypertrophy. Mechanism study demonstrated that JMJD1A promoted the expression and activity of Catalase under basal condition or oxidative stress. siRNA-mediated loss of Catalase blocked the protection of JMJD1A overexpression against ISO-induced cardiomyocyte hypertrophy. These findings demonstrated that JMJD1A loss promoted cardiomyocyte hypertrophy in a Catalase and ROS-dependent manner.

scholarly journals Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Weinian Gao ◽  
Na Guo ◽  
Shuguang Zhao ◽  
Ziying Chen ◽  
Wenli Zhang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Cancer Biology ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Marker Genes ◽  
Mechanism Study ◽  
Rat Cardiomyocytes

Abstract Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Current studies have identified the roles of CPA4 in cancer biology and insulin sensitivity. However, the roles of CPA4 in other diseases are not known. In the present study, we investigated the roles of CPA4 in cardiac hypertrophy. The expression of CPA4 was significantly increased in the hypertrophic heart tissues of human patients and isoproterenol (ISO)-induced hypertrophic heart tissues of mice. We next knocked down Cpa4 with shRNA or overexpressed Cpa4 using adenovirus in neonatal rat cardiomyocytes and induced cardiomyocyte hypertrophy with ISO. We observed that Cpa4 overexpression promoted whereas Cpa4 knockdown reduced ISO-induced growth of cardiomyocyte size and overexpression of hypertrophy marker genes, such as myosin heavy chain β (β-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp). Our further mechanism study revealed that the mammalian target of rapamycin (mTOR) signaling was activated by Cpa4 in cardiomyocytes, which depended on the phosphoinositide 3-kinase (PI3K)-AKT signaling. Besides, we showed that the PI3K-AKT-mTOR signaling was critically involved in the roles of Cpa4 during cardiomyocyte hypertrophy. Collectively, these results demonstrated that CPA4 is a regulator of cardiac hypertrophy by activating the PI3K-AKT-mTOR signaling, and CPA4 may serve as a promising target for the treatment of hypertrophic cardiac diseases.

scholarly journals Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Maomao Gao ◽  
Fengjiao Hu ◽  
Manli Hu ◽  
Yufeng Hu ◽  
Hongjie Shi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibrosis ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
Compound C

Abstract Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination. Results: Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy. Conclusion: Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.

Upregulation of α-enolase protects cardiomyocytes from phenylephrine-induced hypertrophy

2018 ◽  
Vol 96 (4) ◽  
pp. 352-358
Author(s):  
Si Gao ◽  
Xue-ping Liu ◽  
Li-hua Wei ◽  
Jing Lu ◽  
Peiqing Liu
Keyword(s):  
Cardiac Hypertrophy ◽  
Glycolytic Enzyme ◽  
Pathological Process ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Abnormal Growth ◽  
Protein Levels ◽  
Neonatal Rat Cardiomyocytes ◽  
Abdominal Aortic

Cardiac hypertrophy often refers to the abnormal growth of heart muscle through a variety of factors. The mechanisms of cardiomyocyte hypertrophy have been extensively investigated using neonatal rat cardiomyocytes treated with phenylephrine. α-Enolase is a glycolytic enzyme with “multifunctional jobs” beyond its catalytic activity. Its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the change of α-enolase during cardiac hypertrophy and explore its role in this pathological process. We revealed that mRNA and protein levels of α-enolase were significantly upregulated in hypertrophic rat heart induced by abdominal aortic constriction and in phenylephrine-treated neonatal rat cardiomyocytes. Furthermore, knockdown of α-enolase by RNA interference in cardiomyocytes mimicked the hypertrophic responses and aggravated phenylephrine-induced hypertrophy without reducing the total glycolytic activity of enolase. In addition, knockdown of α-enolase led to an increase of GATA4 expression in the normal and phenylephrine-treated cardiomyocytes. Our results suggest that the elevation of α-enolase during cardiac hypertrophy is compensatory. It exerts a catalytic independent role in protecting cardiomyocytes against pathological hypertrophy.

Abstract 934: Contributory Role of VEGF Overexpression in Endothelin-1-induced Cardiomyocyte Hypertrophy: Involvement of Hyopoxia Inducible Factor

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nobutake Shimojo ◽  
Subrina Jesmin ◽  
Yuichi Hattori ◽  
Seiji Maeda ◽  
Takashi Miyauchi ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hypoxia Inducible Factor ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Cardiomyocytes ◽  
Endothelin 1 ◽  
Vegf Signaling ◽  
Endothelial Growth Factor

Although endothelin-1 (ET-1) stimulates vascular endothelial growth factor (VEGF) expression in a variety of cells, including endothelial cells and vascular smooth muscle cells, the effect of ET-1 on expression of VEGF and its receptors in cardiomyocytes is unknown. In the present study, we found that treatment of neonatal rat cardiomyocytes with ET-1 for 24 h resulted in upregulation of VEGF and its two principle receptors, fetal liver kinase (flk)-1 and fms-like tyrosine kinase (flt)-1, in a concentration-dependent manner (10 −12 -10 −6 M). ET-1 treatment also caused significant cardiomyocyte hypertrophy, as indicated by increases in cell surface area (2.0-fold compared to control) and 14 C-leucine uptake (1.8 fold) by cardiomyocytes. And this ET-1 mediated upregulation of VEGF in cardiomyocytes was associated with the induction of hypoxia inducible factor (HIF)-1β and HIF-2α, not HIF-1α. Treatment with TA-0201 (10 −6 M), an ET A selective blocker, eliminated ET-1-induced overexpression of VEGF and its receptors as well as cardiomyocyte hypertrophy. Treatment with VEGF neutralizing peptides (5–10 μg/ml) partially but significantly inhibited ET-1-induced cardiomyocyte hypertrophy. Both TA-0201 and VEGF neutralizing peptides also significantly prevented the increase of phosphorylated KDR, which implies the activation of VEGF system in ET-1 induced hypertrophied cardiomyocyte. These results suggest that ET-1 treatment of cardiomyocytes promotes overexpression of VEGF and its receptors via activation of ET A receptors, and consequently the upregulated VEGF signaling system appears to contribute, at least in part, to ET-1-induced cardiomyocyte hypertrophy.

Abstract 182: CTRP9 - A Novel Cardiac Derived Secreted Factor With Anti-hypertrophic Properties

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Astrid H Breitbart ◽  
Florian Brandes ◽  
Oliver Müller ◽  
Natali Froese ◽  
Mortimer Korf-Klingebiel ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Real Time ◽  
Real Time Pcr ◽  
Weight Ratio ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Quantitative Real Time Pcr ◽  
Rat Cardiomyocytes ◽  
Knock Out

Background: CTRP9 (also called C1qtnf9) is a newly discovered secreted protein and a paralog of adiponectin. The biological functions of CTRP9, however, are still largely unknown. Results: Although previous data from a semi-quantitative real-time PCR had suggested that CTRP9 is mainly secreted by adipose tissue, we found its mRNA to be predominantly expressed in the heart by quantitative real-time PCR. Interestingly, we identified CTRP9 mRNA as significantly upregulated in hypertrophied mouse hearts (after 2 weeks of aortic constriction, TAC) as well as in hypertrophied human hearts (24±4-fold versus healthy human myocardium; p<0.01). LacZ staining in myocardial sections of C1qtnf9 tm1(KOMP)Vlcg mice (knock-out for CTRP9, containing a lacZ cassette to replace exon 1-3 of the gene) revealed exclusive expression of CTRP9 in capillary and venous endothelial cells. Adenoviral overexpression of CTRP9 or recombinant CTRP9 strongly inhibited cardiomyocyte hypertrophy (assessed as cell size, protein/DNA-ratio, expression of skeletal α-actin) after stimulation with phenylephrine (PE). Accordingly, myocardial overexpression of CTRP9 via a cardioselective adeno-associated virus (AAV9-CTRP9) in mice dramatically reduced cardiac hypertrophy after two weeks of pressure overload (heart weight/body weight ratio, HW/BW in mg/g: AAV9-control 6.5±0.2 versus AAV9-CTRP9 5.6±0.2; p<0.01). In turn, downregulation of CTRP9 by a specific siRNA aggravated cardiomyocyte growth in response to PE in vitro and CTRP9 knock-out (KO) mice exerted an enhanced hypertrophic response after two weeks of TAC in vivo (% increase in HW/BW versus sham: wild-type 77±13, KO 106±9; p<0.05). Mechanistically, we found that CTRP9 binds to the adiponectin receptor 1 (AdipoR1) and inhibits prohypertrophic mTOR signalling in cardiac myocytes. SiRNA mediated downregulation of AdipoR1 or mTOR in neonatal rat cardiomyocytes abolished the anti-hypertrophic effect of CTRP9. Conclusion: Endothelial cell derived CTRP9 inhibits cardiac hypertrophy through binding to AdipoR1 and inhibition of the mTOR pathway in cardiomyocytes. Therefore, myocardial application of CTRP9 could be a novel strategy to combat pathological cardiac hypertrophy.

scholarly journals Lycopene Inhibits Urotensin-II-Induced Cardiomyocyte Hypertrophy in Neonatal Rat Cardiomyocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hung-Hsing Chao ◽  
Li-Chin Sung ◽  
Cheng-Hsien Chen ◽  
Ju-Chi Liu ◽  
Jin-Jer Chen ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Activity Level ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Urotensin Ii ◽  
Rat Cardiomyocytes ◽  
Protein Levels ◽  
Neonatal Rat Cardiomyocytes ◽  
Tensin Homolog

This study investigated how lycopene affected urotensin-II- (U-II-) induced cardiomyocyte hypertrophy and the possible implicated mechanisms. Neonatal rat cardiomyocytes were exposed to U-II (1 nM) either exclusively or following 6 h of lycopene pretreatment (1–10 μM). The lycopene (3–10 μM) pretreatment significantly inhibited the U-II-induced cardiomyocyte hypertrophy, decreased the production of U-II-induced reactive oxygen species (ROS), and reduced the level of NAD(P)H oxidase-4 expression. Lycopene further inhibited the U-II-induced phosphorylation of the redox-sensitive extracellular signal-regulated kinases. Moreover, lycopene treatment prevented the increase in the phosphorylation of serine-threonine kinase Akt and glycogen synthase kinase-3beta (GSK-3β) caused by U-II without affecting the protein levels of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN). However, lycopene increased the PTEN activity level, suggesting that lycopene prevents ROS-induced PTEN inactivation. These findings imply that lycopene yields antihypertrophic effects that can prevent the activation of the Akt/GSK-3βhypertrophic pathway by modulating PTEN inactivation through U-II treatment. Thus, the data indicate that lycopene prevented U-II-induced cardiomyocyte hypertrophy through a mechanism involving the inhibition of redox signaling. These findings provide novel data regarding the molecular mechanisms by which lycopene regulates cardiomyocyte hypertrophy.

Abstract 72: Hydrogen Sulfide Prevents Myocardial Hypertrophy in a Klf5-dependent Manner

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Guoliang Meng ◽  
Liping Xie ◽  
Yong Ji
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Promoter Activity ◽  
Myocardial Hypertrophy ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Ang Ii ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Cardiomyocytes

Rationale: H 2 S is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like transcription factor (KLF) exerts diverse functions in the cardiovascular system. Objectives: The aim of present study was to investigate the effect of hydrogen sulfide (H 2 S) on myocardial hypertrophy. Methods and results: Myocardial samples of 22 patients with left ventricle hypertrophy were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats (SHR) and neonatal rat cardiomyocytes were studied for functional and signaling response to GYY4137, a H 2 S-releasing compound. Expression of cystathionine -lyase (CSE), a main enzyme for H 2 S generation in human heart, decreased in human hypertrophic myocardium, while KLF5 expression increased. In SHR treated with GYY4137 for 4 weeks, myocardial hypertrophy was inhibited as evidenced by improvement in cardiac structural parameters, heart mass index, size of cardiac myocytes and expression of atrial natriuretic peptide (ANP). Levels of oxidative stress and phosphorylation of mitogen-activated protein kinases were also decreased after H 2 S treatment. H 2 S diminished expression of the KLF5 in myocardium of SHR and in neonatal rat cardiomyocytes rendered hypertrophy by angiotensin II (Ang II). H 2 S also inhibited ANP promoter activity and ANP expression in Ang II-induced neonatal rat cardiomyocyte hypertrophy, and these effects were suppressed by KLF5 knockdown. KLF5 promoter activity was increased by Ang II stimulation, and this was reversed by H 2 S. H 2 S also decreased activity of specificity protein-1 (SP-1) binding to the KLF5 promoter and attenuated KLF5 nuclear translocation by Ang II stimulation. Conclusion: H 2 S attenuated myocardial hypertrophy, which might be related to inhibiting oxidative stress and decreasing ANP transcription activity in a KLF5-dependent manner.

Abstract 541: Dyxin/Lmcd1, A Novel LIM Protein, Is Both Necessary And Sufficient For The Induction Of Cardiomyocyte Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Derk Frank ◽  
Christiane Hanselmann ◽  
Rainer Will ◽  
Hugo A Katus ◽  
Norbert Frey
Keyword(s):  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Hypertrophic Response ◽  
Lim Protein ◽  
A Genome ◽  
Necessary And Sufficient

Sustained cardiac hypertrophy may lead to heart failure and sudden death. While significant progress has been made in elucidating the underlying molecular mechanisms, it is believed that several molecules that modulate cardiomyocyte growth remain elusive. To identify novel candidates involved in hypertrophic signalling, we conducted a genome-wide screening experiment by subjecting neonatal rat cardiomyocytes (NRCM) to either biomechanical stretch or phenylephrine (PE) stimulation followed by microarray analyses. Among several other molecules (stretch: n=164; PE: n=238), the new LIM protein Dyxin/Lmcd1 was significantly upregulated both by stretch (5.6fold, p<0.001) and PE (2.5 fold, p<0.01). Moreover, Dyxin was markedly induced in hypertrophic hearts of transgenic mice overexpressing the phosphatase calcineurin (3.8fold on mRNA- and 2.9fold on protein level (both p<0.01)). To dissect the putative function of this novel molecule, we adenovirally overexpressed Dyxin in NRCM, which led to marked cellular hypertrophy (1.5fold increase in cell surface area, p<0.001) and induction of ANF (3.8fold, p<0.05). In addition, the calcineurin-responsive gene MCIP1.4 was found upregulated (3.2fold, p<0.001), suggesting that Dyxin activates the calcineurin pathway. In order to test whether Dyxin is also required for cardiomyocyte hypertrophy, we stimulated NRCVM with either PE or stretch and utilized adenovirus-encoded microRNAs to knock down Dyxin (−75% on protein, −85% on mRNA level). While both PE and stretch induced significant hypertrophy (+41% and +48%, p<0.001), the inhibition of Dyxin expression completely blunted the hypertrophic response to both stimuli (p<0.001). Consistently, induction of the “hypertrophic gene program” (including ANF, BNP, and alpha-skeletal actin) was abrogated. Likewise, PE-mediated upregulation of MCIP1.4 expression (7.3fold; p<0.001), was entirely prevented by the knockdown of Dyxin (0.8fold, p=n.s.). We show here that Dyxin, which has not been implicated in hypertrophy before, is significantly upregulated in cardiac hypertrophy. Moreover, it is both necessary and sufficient for cardiomyocyte hypertrophy, and this effect is mediated, at least in part by modulation of calcineurin signalling.

Abstract 1828: Dyxin/Lmcd1 Mediates Cardiac Hypertrophy Both In Vitro And In Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Derk Frank ◽  
Robert Frauen ◽  
Christiane Hanselmann ◽  
Christian Kuhn ◽  
Rainer Will ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
The Novel ◽  
Rat Cardiomyocytes ◽  
A Genome

In order to identify new molecular mediators of cardiomyocyte hypertrophy, we performed a genome wide mRNA microarray screen of biomechanically stretched neonatal rat cardiomyocytes (NRCM). We found the novel sarcomeric LIM protein Dyxin/Lmcd1 being significantly upregulated (5.6x, p<0.001). Moreover, Dyxin was also significantly induced in several mouse models of myocardial hypertrophy including aortic banding, calcineurin overexpression and angiotensin stimulation, suggesting a potential role as a mediator of cardiac hypertrophy. To further test this hypothesis, we adenovirally overexpressed Dyxin in NRCM which potently induced cellular hypertrophy (150%, p<0.001) and the hypertrophic gene program (ANF, BNP). Consistent with an induction of calcineurin signalling, the calcineurin-responsive gene Rcan1– 4 (MCIP1.4) was found significantly upregulated (3.2x, p<0.001). Conversely, knockdown of Dyxin (−75% on protein level) via miRNA completely blunted the hypertrophic response to hypertrophic stimuli, including stretch and PE (both p<0.001). Furthermore, PE-mediated activation of calcineurin signaling (Upregulation of Rcan1– 4 by 7.3x, p<0.001) was completely blocked by knockdown of Dyxin. To confirm these results in vivo, we next generated transgenic mice with cardiac-restricted overexpression of Dyxin using the α -MHC promoter. Despite normal cardiac function as assessed by echocardiography, adult transgenic mice displayed significant cardiac hypertrophy in morphometrical analyses (3.9 vs. 3.5 mg/g LV/heart weight, n=8–11, p<0.05). This finding was supplemented by a robust induction of the hypertrophic gene program including ANF (3.7-fold, n=6, p=0.01) and α -skeletal actin (2.8-fold, n=6, p<0.05). Likewise, Rcan1– 4 was found upregulated (+112%, n=5, p<0.05), Taken together, we show that the novel sarcomeric z-disc protein Dyxin/Lmcd1 is significantly upregulated in several models of cardiac hypertrophy and potently induces cardiomyocyte hypertrophy both in vitro and in vivo. Mechanistically, Lmcd1/Dyxin appears to signal through the calcineurin pathway.

mTOR signaling-related microRNAs as cardiac hypertrophy modulators in high‐volume endurance training

2021 ◽  
Author(s):  
Bruno R.A. Pelozin ◽  
Ursula Paula Reno Soci ◽  
João L. P. Gomes ◽  
Edilamar Menezes Oliveira ◽  
Tiago Fernandes
Keyword(s):  
Protein Expression ◽  
Molecular Mechanisms ◽  
High Volume ◽  
Left Ventricular ◽  
Mtor Signaling ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Peak Exercise ◽  
Dependent Manner ◽  
Rat Cardiomyocytes

Aerobic exercise training (ET) promotes cardiovascular adaptations, including physiological left ventricular hypertrophy (LVH). However, the molecular mechanisms that underlying these changes are unclear. The study aimed to elucidate specific miRNAs and target genes involved with the Akt/mTOR signaling in high-volume ET-induced LVH. Eight-week-old female Wistar rats were assigned to three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 minutes/day of swimming, 5x/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week; in the 9th week, rats trained 2x/day, and in the 10th week, trained 3x/day. Subsequently, structure and molecular parameters were evaluated in the heart. Trained groups demonstrate higher values to VO2 peak, exercise tolerance, and LVH in a volume-dependent manner. The miRNA-26a-5p levels were higher in P1 and P2 compared to SC group (150±15%, d=1.8; 148±16%, d=1.7; and 100±7%, respectively, P < 0.05). In contrast, miRNA-16-5p levels were lower in P1 and P2 compared to SC group (69±5%, d=2.3, P < 0.01; 37±4%, d=5.6, P < 0.001 and 100±6%, respectively). Additionally, miRNA-16-5p knockdown and miRNA-26a-5p overexpression significantly promoted cardiomyocyte hypertrophy in neonatal rat cardiomyocytes. Both miRNAs were selected, using Diana Tolls bioinformatics website, for acting in the mTOR signaling pathway. The protein expression of Akt, mTOR, p70S6k, and 4E-BP1 were greater in P1 and even more pronounced in P2. Nonetheless, GSK3β protein expression was lower in trained groups. Together, these molecular changes may contribute to a pronounced physiological LVH observed in high-volume aerobic training.

Sign in / Sign up

Export Citation Format

Share Document