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Glutathione S-Transferase α4 Alleviates Hyperlipidemia-Induced Vascular Neointimal Hyperplasia in Arteriovenous Grafts via Inhibiting Endoplasmic Reticulum Stress.
Zhou, Chenchen; Zhong, Yanxia; Chu, Yun; Chen, Renyu; Wang, Yurou; Zheng, Yingfang; Dai, Hongkai; Zhan, Chengye; Xie, Aini; Luo, Jinlong.
Afiliación
  • Zhou C; Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhong Y; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Chu Y; Intensive Care Unit, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ; and.
  • Chen R; Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang Y; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zheng Y; Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Dai H; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhan C; Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Xie A; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Luo J; Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cardiovasc Pharmacol ; 84(1): 58-70, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38573593
ABSTRACT
ABSTRACT Neointimal hyperplasia causes the failure of coronary artery bypass grafting. Our previous studies have found that endothelial dysfunction is 1 candidate for triggering neointimal hyperplasia, but which factors are involved in this process is unclear. Glutathione S-transferase α4 (GSTA4) plays an important role in metabolizing 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product, which causes endothelial dysfunction or death. Here, we investigated the role of GSTA4 in neointima formation after arteriovenous grafts (AVGs) with or without high-fat diet (HFD). Compared with normal diet, HFD caused endothelial dysfunction and increased neointima formation, concomitantly accompanied by downregulated expression of GSTA4 at the mRNA and protein levels. In vitro, overexpression of GSTA4 attenuated 4-HNE-induced endothelial dysfunction and knockdown of GSTA4 aggravated endothelial dysfunction. Furthermore, silencing GSTA4 expression facilitated the activation of 4-HNE-induced endoplasmic reticulum stress and inhibition of endoplasmic reticulum stress pathway alleviated 4-HNE-induced endothelial dysfunction. In addition, compared with wild-type mice, mice with knockout of endothelial-specific GSTA4 (GSTA4 endothelial cell KO) exhibited exacerbated vascular endothelial dysfunction and increased neointima formation caused by HFD. Together, these results demonstrate the critical role of GSTA4 in protecting the function of endothelial cells and in alleviating hyperlipidemia-induced vascular neointimal hyperplasia in arteriovenous grafts.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Modelos Animales de Enfermedad / Neointima / Estrés del Retículo Endoplásmico / Glutatión Transferasa / Hiperlipidemias / Hiperplasia / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: J Cardiovasc Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Modelos Animales de Enfermedad / Neointima / Estrés del Retículo Endoplásmico / Glutatión Transferasa / Hiperlipidemias / Hiperplasia / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: J Cardiovasc Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos