Decrease in Caveolae-Gαq Interaction Mediates Pressure Overload-Induced Cardiac Remodeling in Rats.

Abstract

Despite its significant clinical implications, pressure overload-induced cardiac remodeling is poorly understood. This study aimed to investigate the role of Caveolae-Gαq interaction in the pathophysiology of pressure overload-induced cardiac remodeling. We used the abdominal aortic constriction (AAC) rat model and the angiotensin II-treated cell model to simulate pressure overload-induced cardiac remodeling. Histological changes were assessed using hematoxylin-eosin staining, immunofluorescence staining, and transmission electron microscopy. The expression, colocalization, and calcium response of the Caveolae-Gαq-PLCβ3 signaling pathway were evaluated using western blotting, quantitative real-time PCR, immunofluorescence staining, and calcium green labeling. We found AAC decreased Caveolin-3 expression but increased Gαq and PLCβ3 expressions. Similar trends in mRNA expression levels were observed. The caveolae's ultrastructure was deformed at 4 and 12 weeks after AAC surgery. AAC and angiotensin II treatments reduced Caveolin-3 and Gαq colocalization while increasing Gαq and PLCβ3 colocalization, and prolonging intracellular calcium response after Gαq activation. In conclusion, pressure overload-induced cardiac remodeling involves caveolar deformation and decreased Caveolae-Gαq interactions, which result in enhanced expression and functionality of Gαq-PLCβ3 signaling. These findings highlight the mechanistic importance of Caveolae-Gαq interactions in cardiac hypertrophy under pressure overload conditions.