Ang II-induced Pathological Autophagy is Inhibited by IL-10 via Akt Dependent Inhibition of Beclin 1 in Mice Heart

Although, autophagy is an essential cellular salvage process to maintain cellular homeostasis, pathological autophagy can lead to cardiac abnormalities and ultimately heart failure. Therefore, a tight regulation on autophagic process would be important to treat chronic heart failure. Previously, we have shown that IL-10 strongly improved cardiac function in chronic heart failure models, but the role of IL-10 in regulation of pathological autophagy is not yet investigated. We tested the hypothesis that IL-10 inhibits angiotensin II-induced pathological autophagy and thus improved cardiac function. Pathological autophagy was induced in wild type (WT) and IL10-knockout mice by angiotensin II infusion. Ang II-induced left ventricular dysfunction and hypertrophic remodeling were accentuated in IL-10 KO mice compared to WT mice. IL-10 KO mice showed exaggerated autophagy with reduced AKT phosphorylation. In neonatal rat ventricular cardiomyocytes, Ang II activated beclin1 and LC3 levels and inhibited AKT/mTORC1...