The mechanism of mitochondrial damage of atrial myocytes mediated by
GSDMD-N promoting atrial remodeling in diabetes
Abstract
Gasdermin D (GSDMD) can induce pyroptosis and mitochondrial damage,
thereby promoting the occurrence and development of diabetes (DM)
related atrial fibrillation (AF). We aimed to investigate the mechanism
of mitochondrial damage in atrial myocytes mediated by GSDMD N-terminal
domain (GSDMD-N) in DM related AF. We established a rat DM model and
demonstrated that under high blood glucose stimulation, the NLRP3
inflammasome pathway can activate GSDMD into active GSDMD-N, thereby
exacerbating mitochondrial damage and pyroptosis of atrial myocytes in
DM rats, leading to atrial remodeling. Meanwhile, DM can act on
fibroblasts, promote collagen synthesis and inhibit its breakdown, and
lead to myocardial fibrosis. In addition, inflammation and oxidative
stress mediated by DM can promote atrial electrical remodeling, while
changes in myocardial cell ultrastructure caused by myocardial fibrosis
and pyroptosis can also exacerbate electrical remodeling. The
interaction between structural reconstruction and electrical
reconstruction jointly promotes the occurrence and development of AF.