Dataset Information

MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4.

ABSTRACT: Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to overload pressure of heart. From abundant studies, a conclusion is drawn that many microRNAs (miRNAs) are associated with cardiac hypertrophy and heart failure. To investigate the role of microRNA-497 (miR-497) in myocardial hypertrophy, two models were established in this study from cell level to integral level. Cardiac hypertrophy was induced by using angiotensin ? (Ang ?) in vitro and was created by transverse abdominal aortic constriction (TAC) in vivo. There was a significant decrease expression of miR-497 in cardiac hypertrophy models. Moreover, overexpression of miR-497 inhibited myocardial hypertrophy both in vitro and in vivo without heart function variation. In addition, luciferase reporter assays demonstrated that Sirt4 was a direct target gene of miR-497. Taking together, our study indicates that miR-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC5161464 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4.

Xiao Yimin Y Zhang Xiaofei X Fan Shihao S Cui Guanghao G Shen Zhenya Z

PloS one 20161216 12

Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to overload pressure of heart. From abundant studies, a conclusion is drawn that many microRNAs (miRNAs) are associated with cardiac hypertrophy and heart failure. To investigate the role of microRNA-497 (miR-497) in myocardial hypertrophy, two models were established in this study from cell level to integral level. Cardiac hypertrophy was induced by using angiotensin Ⅱ (Ang Ⅱ) in vitro and was created by transverse abd ...[more]

PMID: 27992564

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Project description:BackgroundPathological cardiac hypertrophy occurs in response to numerous stimuli and precedes heart failure (HF). Therapies that ameliorate pathological cardiac hypertrophy are highly needed.MethodsThe expression level of miR-30d was analyzed in hypertrophy models and serum of patients with chronic heart failure by qRT-PCR. Gain and loss-of-function experiments of miR-30d were performed in vitro. miR-30d gain of function were performed in vivo. Bioinformatics, western blot, luciferase assay, qRT-PCR, and immunofluorescence were performed to examine the molecular mechanisms of miR-30d.FindingsmiR-30d was decreased in both murine and neonatal rat cardiomyocytes (NRCMs) models of hypertrophy. miR-30d overexpression ameliorated phenylephrine (PE) and angiotensin II (Ang II) induced hypertrophy in NRCMs, whereas the opposite phenotype was observed when miR-30d was downregulated. Consistently, the miR-30d transgenic rat was found to protect against isoproterenol (ISO)-induced pathological hypertrophy. Mechanistically, methyltransferase EZH2 could promote H3K27me3 methylation in the promotor region of miR-30d and suppress its expression during the pathological cardiac hypertrophy. miR-30d prevented pathological cardiac hypertrophy via negatively regulating its target genes MAP4K4 and GRP78 and inhibiting pro-hypertrophic nuclear factor of activated T cells (NFAT). Adeno-associated virus (AAV) serotype 9 mediated-miR-30d overexpression exhibited beneficial effects in murine hypertrophic model. Notably, miR-30d was reduced in serum of patients with chronic heart failure and miR-30d overexpression could significantly ameliorate pathological hypertrophy in human embryonic stem cell-derived cardiomyocytes.InterpretationOverexpression of miR-30d may be a potential approach to treat pathological cardiac hypertrophy.FundingThis work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to J Xiao), National Natural Science Foundation of China (82020108002 to J Xiao, 81900359 to J Li), the grant from Science and Technology Commission of Shanghai Municipality (20DZ2255400 and 21XD1421300 to J Xiao, 22010500200 to J Li), Shanghai Sailing Program (19YF1416400 to J Li), the "Dawn" Program of Shanghai Education Commission (19SG34 to J Xiao), the "Chen Guang" project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (19CG45 to J Li).

Dataset Information

MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4.

Publications

MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4.

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