PLXND1-mediated calcium dyshomeostasis impairs endocardial endothelial autophagy in atrial fibrillation

• DOI: 10.3389/fphys.2022.960480
• Publication Date: 2022-08-09T04:50:36Z
• Authors: Mengjia Sun; Zhen Chen; Yuanbin Song; Bo Zhang; Jie Yang; Hu Tan
• Keywords: Calcium in biology

Left atrial appendage (LAA) thrombus detachment resulting in intracranial embolism is a major complication of fibrillation (AF). Endocardial endothelial cell (EEC) injury leads to thrombosis, whereas autophagy protects against EEC dysfunction. However, the role and underlying mechanisms EECs during AF have not been elucidated. In this study, we isolated from model mice observed reduced autophagic flux intracellular calcium concentrations mice. addition, detected an increased expression mechanosensitive protein PLXND1 cytomembranes EECs. served as scaffold bind with ORAI1 further decreased ORAI1-mediated influx. The decrease influx-mediated phosphorylation CAMK2 associated inhibition autophagy, which results dysfunction AF. Our study demonstrated that change contributes dyshomeostasis, inhibits This provides potential intervention target for prevent treat intracardiac thrombosis its complications.