Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway

• Autophagy was inhibited in the remodeling hearts induced by pressure overload.
• ALDH2 deficiency exacerbated pressure overload-induced cardiac anomalies.
• ALDH2 deficiency accentuated pressure overload-induced suppression of autophagy.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2 −/− mice in HE-stained myocardial tissue samples at 8 weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2 −/− TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8 weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway.This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.