Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy
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 dysfunc...
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Veröffentlicht in: | Bioscience reports 2019-12, Vol.39 (12) |
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Sprache: | eng |
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Zusammenfassung: | 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 AMPKα2 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. |
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ISSN: | 0144-8463 1573-4935 |
DOI: | 10.1042/BSR20191860 |