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Angiopoietin-like protein 8 deficiency attenuates thoracic aortic aneurysm/dissection development in ß-aminopropionitrile monofumarate-induced model mice.
Yang, Yun-Yun; Jiao, Xiao-Lu; Yu, Hua-Hui; Li, Lin-Yi; Li, Juan; Zhang, Xiao-Ping; Qin, Yan-Wen.
Afiliación
  • Yang YY; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing 100
  • Jiao XL; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • Yu HH; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • Li LY; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • Li J; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • Zhang XP; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • Qin YW; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. Electronic address: qinyanwen@ccmu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1869(2): 166619, 2023 02.
Article en En | MEDLINE | ID: mdl-36494038
Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening cardiovascular disorder. Endoplasmic reticulum stress (ERS) and vascular smooth muscle cell (VSMC) apoptosis are involved in TAAD progression. The Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway is associated with VSMC apoptosis. Serum Angiopoietin-Like Protein 8 (ANGPTL8) levels are associated with aortic diameter and rupture rate of TAAD. However, a direct role of ANGPTL8 in TAAD has not been determined. ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAAD in C57BL/6 mice. ANGPTL8 knockout mice were used to detect the effects of ANGPTL8 on TAAD development. ANGPTL8knockdown in vitro was used to analyze the role of ANGPTL8 in VSMCs and ERS. In addition, over-expression of ANGPTL8 in VSMCs and a PERK inhibitor were used to assess the effect of ANGPTL8 on the PERK pathway. ANGPTL8 levels were increased in the aortic wall and VSMCs of BAPN-induced TAAD mice. Compared with BAPN-treated wild-type mice, ANGPTL8 knockout significantly reduced the rupture rate of TAAD to 0 %. In addition, the protein levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP9) and ERS proteins were decreased in the aorta wall. Angptl8 shRNA decreased MMP9 and ERS protein levels in VSMCs in vitro. Overexpression of ANGPTL8 significantly increased the levels of ERS proteins and MMPs, while a PERK inhibitor significantly decreased the effects of ANGPTL8 in VSMCs. ANGPTL8 contributed to TAAD development by inducing ERS activation and degradation of extracellular matrix in the aorta wall. Inhibition of ANGPTL8 may therefore represent a new strategy for TAAD therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aneurisma de la Aorta Torácica / Proteína 8 Similar a la Angiopoyetina / Disección Aórtica Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aneurisma de la Aorta Torácica / Proteína 8 Similar a la Angiopoyetina / Disección Aórtica Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos