LRRC8A contributes to angiotensin II-induced cardiac hypertrophy by interacting with NADPH oxidases via the C-terminal leucine-rich repeat domain.

LRRC8A contributes to angiotensin II-induced cardiac hypertrophy by interacting with NADPH oxidases via the C-terminal leucine-rich repeat domain. Free Radic Biol Med. 2021 Jan 27;: Authors: Huo C, Liu Y, Li X, Xu R, Jia X, Hou L, Wang X Abstract Cardiac hypertrophy, an important cause of heart failure, is characterized by an increase in heart weight, the ventricular wall, and cardiomyocyte volume. The volume regulatory anion channel (VRAC) is an important regulator of cell volume. However, its role in cardiac hypertrophy remains unclear. The purpose of this study was to investigate the effect of leucine-rich repeat-containing 8A (LRRC8A), an essential component of the VRAC, on angiotensin II (AngII)-induced cardiac hypertrophy. Our results showed that LRRC8A expression, NADPH oxidase activity, and reactive oxygen species (ROS) production were increased in AngII-induced hypertrophic neonatal mouse cardiomyocytes and the myocardium of C57/BL/6 mice. In addition, AngII activated VRAC currents in cardiomyocytes. The delivery of adeno-associated viral (AAV9) bearing siRNA against mouse LRRC8A into the left ventricular wall inhibited AngII-induced cardiac hypertrophy and fibrosis. Accordingly, the knockdown of LRRC8A attenuated AngII-induced cardiomyocyte hypertrophy and VRAC currents in vitro. Furthermore, knockdown of LRRC8A suppressed AngII-induced ROS production, NADPH oxidase activity, the expression of NADPH oxidase membrane-bound s...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research