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Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis.

作者:Jia‐Bao Liu, Peng Wu, Yunle Wang, Yingqiang Du, Nan A, Shuiyuan Liu, Yiming Zhang, Ningtian Zhou, Zhihui Xu, Zhijian Yang · 发表于:PubMed · 年份:2016 · 被引用次数:42 · 研究领域:Autophagy in Disease and Therapy、Advanced Glycation End Products research、Cardiovascular Function and Risk Factors

. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling.