G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endothelial Cell Biology

Background:

• GTPase-activating SH3 domain-binding protein 2 (G3BP2) mediates stress responses and chronic disease progression.
• The role of G3BP2 in oscillatory shear stress (OSS)-induced endothelial dysfunction remains unexplored.

Purpose of the Study:

• To investigate the function of G3BP2 in endothelial cells (ECs) under OSS.
• To elucidate the underlying mechanisms of G3BP2's involvement in endothelial dysfunction and atherosclerosis.

Main Methods:

• Utilized shear stress apparatus and partial ligation models in mice.
• Performed RNA sequencing (RNA-seq) to identify stress granule-related genes.
• Assessed endothelial barrier function, monocyte adhesion, and inflammatory cytokine levels.

Main Results:

• OSS induced stress granule-related genes in ECs, with G3BP2 highly expressed in OSS regions.
• G3BP2 deficiency in Apoe-/- mice reduced atherosclerotic lesions, improved endothelial barrier function, decreased monocyte adhesion, and lowered proinflammatory cytokines.
• Loss of G3BP2 diminished OSS-induced EC inflammation by enhancing YAP nucleocytoplasmic shuttling and phosphorylation.

Conclusions:

• G3BP2 is a critical OSS-regulated gene influencing EC function.
• G3BP2 inhibition in ECs represents a potential therapeutic strategy for preventing atherosclerosis.