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- W4256653520 abstract "Rationale: Local flow patterns determine the uneven distribution of atherosclerotic lesions. Sensing mechanical forces, membrane lipid raft and integrin are crucial for shear stress-regulated endothelial function. Objective: In this study, we investigate the role of lipid raft and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under the atheroprone flow. Methods and Results: Lipid raft proteins were isolated from ECs exposed to pulsatile shear stress (PS) or oscillatory shear stress (OS) and then analyzed by quantitative proteomics. Among 396 proteins redistributed in lipid raft, integrin α5 was most significantly elevated in lipid raft under OS. Moreover, OS increased the level of activated integrin α5, which was exclusively located in lipid raft. Disruption of F-actin-based cytoskeleton and knockdown of caveolin-1 prevented the OS-induced integrin α5 translocation and activation, suggesting significant roles of the cytoskeleton and caveolin-1 in integrin α5 translocation. Furthermore, OS activation of integrin α5 induced the NLRP3 inflammasome, leading to increased inflammatory responses. In vivo, activation of integrin α5 and increased expression of adhesion molecules were seen in the atheroprone areas of LDLR-/- mice. Knockdown of integrin α5 greatly attenuated EC dysfunction in partially ligated carotid arteries in LDLR-/-mice. Consistently, genetic ablation of integrin α5 in α5-/- murine embryonic fibroblasts and α5+/- mice caused a reduction of inflammation under the atheroprone flow. Conclusions: Atheroprone flow activates integrin α5 through lipid raft anchoring with ensuing induction of NLRP3 inflammasome in ECs. These findings reveal a novel mechanotransduction mechanism by which atheroprone flow causes endothelial dysfunction." @default.
- W4256653520 created "2022-05-12" @default.
- W4256653520 creator A5084420811 @default.
- W4256653520 creator A5090035031 @default.
- W4256653520 date "2015-05-01" @default.
- W4256653520 modified "2023-09-22" @default.
- W4256653520 title "Abstract 166: Activation of Integrin α5 Mediated by Flow Requires Its Translocation to Membrane Lipid Raft in Vascular Endothelial Cells" @default.
- W4256653520 doi "https://doi.org/10.1161/atvb.35.suppl_1.166" @default.
- W4256653520 hasPublicationYear "2015" @default.
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