G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction

Tianhan Li; Juhui Qiu; Tingting Jia; Yinming Liang; Kun Zhang; Wenhua Yan; Zhengjun Hou; Shiwei Yang; Lushan Liu; Wenhao Xiong; Yaokai Chen; Guixue Wang

doi:10.1016/j.gendis.2021.11.003

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G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction

更新时间：2022-11-09

- G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction
- Genes & Diseases Vol. 9, Issue 6, (2022)
- 作者机构：
  
  1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State Key Laboratory of Mechanical Transmission, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University,Chongqing,PR China,400044
  2. Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University,Henan,Xinxiang,PR China,45003
  3. Department of Vascular Surgery, First Affiliated Hospital, Army Medical University (Third Military University),Chongqing,PR China,400038
  4. Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China,Hunan,Hengyang,PR China,421001
  5. Division of Infectious Diseases, Chongqing Public Health Medical Center,Chongqing,PR China,400030
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.11.003
  CLC：
- Published：2022，
  
  Published Online：1 November 2022，
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Tianhan Li, Juhui Qiu, Tingting Jia, et al. G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction. [J]. Genes & Diseases 9(6).(2022)
DOI：

Tianhan Li, Juhui Qiu, Tingting Jia, et al. G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction. [J]. Genes & Diseases 9(6).(2022) DOI： 10.1016/j.gendis.2021.11.003.

摘要

Abstract

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 granule-related 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.

G3bp2

–/–

Apoe

–/–

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.

关键词

Keywords

AtherosclerosisEndothelial cells (ECs)G3BP2Oscillatory shear stress (OSS)YAP

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