Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis

Significance Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are emerging as key regulators of cell fate in response to biochemical and biophysical cues, but their role in modulating vascular homeostasis in health and disease is not clearly understood. In studying the flow regulation of YAP/TAZ activities in vascular endothelial cells, we find that disturbed flow (without a clear direction), but not laminar flow (with a clear direction), activates YAP/TAZ to promote the atheroprone phenotypes (proliferation and inflammation). We also demonstrate that inhibition of YAP/TAZ attenuates the atheroprone phenotypes and lesion progression in atherosclerotic mice. These findings indicate that YAP/TAZ serve as important mechanotransducers in the disturbed flow-induced atherogenesis and provide insights to the development of therapeutic strategy for cardiovascular diseases.