摘要
GTPase-activating SH3 domain-binding protein 2(G3BP2)is a mediator that responds to environmental stresses through stress granule formation and is involved in the progression of chronic diseases.However,no studies have examined the contribution of G3BP2 in the oscillatory shear stress(OSS)-induced endothelial dysfunction.Here we assessed the effects of G3BP2 in endothelial cells(ECs)function and investigated the underlying mechanism.Using shear stress apparatus and partial ligation model,we identified that stress granulerelated genes in ECs could be induced by OSS with RNA-seq,and then confirmed that G3BP2 was highly and specifically expressed in athero-susceptible endothelia in the OSS regions.G3bp2e/eApoee/e mice had significantly decreased atherosclerotic lesions associated with deficiency of G3BP2 in protecting endothelial barrier function,decreasing monocyte adhesion to ECs and inhibiting the proinflammatory cytokine levels.Furthermore,loss of G3BP2 diminished OSS-induced inflammation in ECs by increasing YAP nucleocytoplasmic shuttling and phosphorylation.These data demonstrate that G3BP2 is a critical OSS regulated gene in regulating ECs function and that G3BP2 inhibition in ECs is a promising atheroprotective therapeutic strategy.
基金
This work was supported by the National Natural Science FoundationofChina(No.31971242 and12032007 toG.W.)
The Natural Science Foundation of Chongqing,China(No.cstc2019jcyj-zdxmX0028 to G.W.,cstc2019jcyj-xfkxX0004 to J.Q.)
Open Fund of Tianjin Enterprise Key Laboratory on Hyaluronic Acid Application Research,China(No.KTRDHAY201903 to G.W.)
The Fundamental Research Funds for the Central Universities,China(No.2019CDYGZD008 to J.Q.)
Chongqing Municipal Education Commission,China(No.KYYJ202001 to G.W.).
