Description

Join us for a webinar with Julia Mack, Ph.D., Assistant Adjunct Professor, UCLA as she presents her talk entitled: "Mechanisms of Endothelial Cell Resilience.”

Abstract:  Endothelial cells in the descending aorta are exposed to high laminar shear stress, which supports an anti-inflammatory phenotype that protects them from atherosclerosis. High laminar shear stress also supports flow-aligned cell elongation and front-rear polarity, but whether this is required for athero-protective signaling is unclear. Here, we show that Caveolin-1-rich microdomains become polarized at the downstream end of arterial endothelial cells exposed to continuous high laminar flow. These microdomains are characterized by higher membrane rigidity, filamentous actin and specific lipid accumulation. Transient receptor potential vanilloid-type 4 (Trpv4) ion channels, while ubiquitously expressed, mediate localized Ca2+ entry at these microdomains. The resultant focal bursts in Ca2+ activate the anti-inflammatory factor endothelial nitric oxide synthase within the confines of these domains. Importantly, we find that signaling at these domains requires both cell body elongation and sustained flow and that Trpv4 signaling at these domains is necessary and sufficient to suppress inflammatory gene expression. Our work reveals a novel polarized mechanosensitive signaling hub that protects arterial endothelial cells from inflammation and promotes cell resilience.