The Degradation of G3BP2 by Trim-away Method Inhibits Oscillatory Shear Stress induced Endothelial Cell Inflammation

Abstract

Abstract Progress in medical science has shown that cardiovascular pathogenesis is a complex disease with multiple underlying factors. Stress factors such as oxidative stress and oscillatory shear stress (OSS) play a crucial role in the occurrence and development of atherosclerosis as the major cause of cardiovascular diseases (CVD). However, study related the effect of stress on the development of human coronary atherosclerosis is not yet fully understood. Ras-GTPase-activating protein SH3 domain-binding proteins 2 (G3BP2) are multi-functional RNA binding proteins in which biomechanically sensitive gene that known important in cancer progression. Here in this study, we further explore the roles of G3BP2 protein especially their relation with atherosclerosis diseases, by investigating the G3BP2 regulation under biomechanical stress stimuli follows with the strategy of exploring the effect of G3BP2 disruption in endothelial cells by the application of new protein depletion technology called Trim-away. The result showed that oxidative stress and oscillatory shear stress (OSS) stimuli activated the expression of G3BP2 protein in primary endothelial cells. Moreover, the western blot analysis revealed that degradation of G3BP2 protein using Trim-away in endothelial cells induced OSS inhibits the release of the pro-inflammatory cytokines (VCAM-1 and ICAM-1). The compelling evidence demonstrated that suppression of G3BP2 protein expression in HUVECs potentially inhibits the development of atherosclerosis by decreased endothelial inflammation response.