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VEGFC ameliorates salt-sensitive hypertension and hypertensive nephropathy by inhibiting NLRP3 inflammasome via activating VEGFR3-AMPK dependent autophagy pathway.
Wu, Qiuwen; Meng, Wei; Zhu, Bin; Chen, Xi; Fu, Jiaxin; Zhao, Chunyu; Liu, Gang; Luo, Xing; Lv, Ying; Zhao, Wenqi; Wang, Fan; Hu, Sining; Zhang, Shuo.
Afiliação
  • Wu Q; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • Meng W; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150001, China.
  • Zhu B; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, 150001, China.
  • Chen X; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • Fu J; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150001, China.
  • Zhao C; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, 150001, China.
  • Liu G; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • Luo X; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150001, China.
  • Lv Y; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, 150001, China.
  • Zhao W; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • Wang F; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150001, China.
  • Hu S; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • Zhang S; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, 150001, China.
Cell Mol Life Sci ; 80(11): 327, 2023 Oct 14.
Article em En | MEDLINE | ID: mdl-37837447
Salt-sensitivity hypertension (SSHTN) is an independent predictor for cardiovascular mortality. VEGFC has been reported to be a protective role in SSHTN and hypertensive kidney injury. However, the underlying mechanisms remain largely unclear. The current study aimed to explore the protective effects and mechanisms of VEGFC against SSHTN and hypertensive nephropathy. Here, we reported that VEGFC attenuated high blood pressure as well as protected against renal inflammation and fibrosis in SSHTN mice. Moreover, VEGFC suppressed the activation of renal NLRP3 inflammasome in SSHTN mice. In vitro, we found VEGFC inhibited NLRP3 inflammasome activation, meanwhile, upregulated autophagy in high-salt-induced macrophages, while these effects were reversed by an autophagy inhibitor 3MA. Furthermore, in vivo, 3MA pretreatment weakened the protective effects of VEGFC on SSHTN and hypertensive nephropathy. Mechanistically, VEGF receptor 3 (VEGFR3) kinase domain activated AMPK by promoting the phosphorylation at Thr183 via binding to AMPK, thus enhancing autophagy activity in the context of high-salt-induced macrophages. These findings indicated that VEGFC inhibited NLRP3 inflammasome activation by promoting VEGFR3-AMPK-dependent autophagy pathway in high-salt-induced macrophages, which provided a mechanistic basis for the therapeutic target in SSHTN and hypertensive kidney injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inflamassomos / Hipertensão Limite: Animals Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inflamassomos / Hipertensão Limite: Animals Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China