Mechanotransduction in Endothelial Cells in Health and Disease
Dr. Shu Chien is University Professor of Bioengineering and Medicine, Director of the Institute of Engineering in Medicine at the University of California, San Diego, and Director of Bioengineering at the Institute of California for the UC System. He is a world leader in molecular, cellular and integrative studies on bioengineering and physiology in health and disease, with research focuses on mechanotransduction, mechanism of regulation of gene expression and stem cell bioengineering. Dr. Chien has published more than 500 papers in peer-reviewed journals and has edited 12 books. He has received outstanding teacher awards at Columbia University and UCSD. Several research awards and student classes have been named after him.
Abstract: Vascular endothelial cells (ECs) play significant roles in regulating circulatory homeostasis in physiological and pathophysiological states. The shear stress resulting from circulatory flow modulates EC functions by activating mechano-sensors, signaling pathways, and gene and protein expressions. Sustained shear stress with a clear direction (e.g., the pulsatile shear stress, PS, in the straight part of the arterial tree) down-regulates the molecular signaling of pro-inflammatory and proliferative pathways. In contrast, shear stress without a definitive direction (e.g., the disturbed or oscillatory flow, OS, at branch points and other regions of complex geometry) causes sustained molecular signaling of pro-inflammatory and proliferative pathways. The EC responses to directed mechanical stimuli involve the remodeling of EC structure to minimize alterations in intracellular stress/strain and elicit adaptive changes in EC signaling in the face of sustained stimuli; these cellular events constitute a feedback control mechanism to maintain vascular homeostasis and are athero-protective. Such a feedback mechanism does not operate effectively in regions of complex geometry, where the mechanical stimuli do not have clear directions, thus placing these areas at risk for atherogenesis.
This Provost’s Lecture will be held on Thursday, May 28, at 11 am in the Charles B. Wang Center Theater.