Abstract 427: Flow Regulation of YAP/TAZ in Endothelial Inflammation and Atherosclerosis

The focal nature of atherosclerotic lesions in regions such as arterial branch points and curvatures suggests a regulatory mechanism by local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechano-transduction and vascular homeostasis. However, the mechanism by which YAP/TAZ modulates endothelial phenotypes in response to atheroprone vs. atheroprotective hemodynamic flows remains unknown. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of endothelial inflammation and the consequential development of atherosclerotic lesions. Experiments were conducted on cultured vascular endothelial cells (ECs) and atherosclerotic mouse model. We found that exposure of ECs to the atheroprone oscillatory shear stress (OS) results in YAP/TAZ activation and translocation into EC nucleus to upregulate the target genes, including connective ti...