Dataset Information

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

ABSTRACT:

Aim

In this work, we explored the role of corosolic acid (CRA) during pressure overload-induced cardiac hypertrophy.

Methods and results

Cardiac hypertrophy was induced in mice by aortic banding. Four weeks post-surgery, CRA-treated mice developed blunted cardiac hypertrophy, fibrosis, and dysfunction, and showed increased LC3 II and p-AMPK expression. In line with the in vivo studies, CRA also inhibited the hypertrophic response induced by PE stimulation accompanying with increased LC3 II and p-AMPK expression. It was also found that CRA blunted cardiomyocyte hypertrophy and promoted autophagy in Angiotensin II (Ang II)-treated H9c2 cells. Moreover, to further verify whether CRA inhibits cardiac hypertrophy by the activation of autophagy, blockade of autophagy was achieved by CQ (an inhibitor of the fusion between autophagosomes and lysosomes) or 3-MA (an inhibitor of autophagosome formation). It was found that autophagy inhibition counteracts the protective effect of CRA on cardiac hypertrophy. Interestingly, AMPK knockdown with AMPK?2 siRNA-counteracted LC3 II expression increase and the hypertrophic response inhibition caused by CRA in PE-treated H9c2 cells.

Conclusion

These results suggest that CRA may protect against cardiac hypertrophy through regulating AMPK-dependent autophagy.

SUBMITTER: Wang ZP

PROVIDER: S-EPMC6893168 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

Wang Zhao-Peng ZP Shen Difei D Che Yan Y Jin Ya-Ge YG Wang Sha-Sha SS Wu Qing-Qing QQ Zhou Heng H Meng Yan-Yan YY Yuan Yuan Y

Bioscience reports 20191201 12

<h4>Aim</h4>In this work, we explored the role of corosolic acid (CRA) during pressure overload-induced cardiac hypertrophy.<h4>Methods and results</h4>Cardiac hypertrophy was induced in mice by aortic banding. Four weeks post-surgery, CRA-treated mice developed blunted cardiac hypertrophy, fibrosis, and dysfunction, and showed increased LC3 II and p-AMPK expression. In line with the in vivo studies, CRA also inhibited the hypertrophic response induced by PE stimulation accompanying with increas ...[more]

PMID: 31746323

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Project description:BackgroundPathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human's health world widely. Deregulation of m6A RNA methylation, and m6A methyltransferases and de-methyltransferases have been demonstrated to act essential roles in cardiac hypertrophy and HF. Here, we studied the potential roles and its underlying mechanisms of m6A Reader YTHDF proteins in HF. In this study, we constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated and stimulated with isoproterenol (ISO) or phenylephrine (PHE) to induce myocardial hypertrophy.ResultsThrough single-cell RNA-seq analysis, immunofluorescent staining, HE staining, Western blotting, and real time-PCR detections, we found that YTHDF2 mRNA and protein level, but not YTHDF1 or YTHDF3, was significantly increased during HF development. YTHDF2 overexpression could efficiently alleviate cardiac hypertrophy. Furthermore, through immunoprecipitation accompanied with mass spectrometry analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that ISO stimulation did not evidently affect YTHDF2-interacting proteins. However, ISO or PHE stimulation significantly increased YTHDF2 protein interacting with Myh7 (beta-myosin heavy chain) mRNA, an important cardiac hypertrophy marker, in an m6A-dependent manner. Knockdown of Myh7 or deletion of the YTH domain of YTHDF2 reversed the protective effects of YTHDF2 on cardiac hypertrophy. Finally, we found that ISO or PHE stimulation promoted YTHDF2 protein expression through enhancing Ythdf2 mRNA stability in an m6A-dependent manner in cardiomyocytes.ConclusionsOverall, our results indicate that the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myh7 mRNA decoy in an m6A-dependent manner. This study highlights the functional importance of YTHDF2-dependent cardiac m6A mRNA regulation during cardiac hypertrophy, and provides a novel mechanistic insight into the therapeutic mechanisms of YTHDF2.

Dataset Information

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

Aim

Methods and results

Conclusion

Publications

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

Similar Datasets

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