Your browser doesn't support javascript.
loading
Phosphate burden induces vascular calcification through a NLRP3-caspase-1-mediated pyroptotic pathway.
Ho, Li-Chun; Chen, Yu-Hsin; Wu, Ting-Yun; Kao, Ling-Zhen; Hung, Shih-Yuan; Liou, Hung-Hsiang; Chen, Pei-Chun; Tsai, Pei-Jane; Lin, Hui-Kuan; Lee, Yi-Che; Wang, Hsi-Hao; Tsai, Yau-Sheng.
Afiliación
  • Ho LC; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; Division of General Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Electronic address: hoim7024@ms3.hinet.net.
  • Chen YH; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Wu TY; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Kao LZ; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Hung SY; Division of Nephrology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
  • Liou HH; Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan.
  • Chen PC; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Tsai PJ; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC, USA.
  • Lin HK; Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC, USA.
  • Lee YC; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
  • Wang HH; Division of Nephrology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
  • Tsai YS; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC, USA; Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan, T
Life Sci ; 332: 122123, 2023 Nov 01.
Article en En | MEDLINE | ID: mdl-37742736
AIMS: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification. MAIN METHODS: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification. KEY FINDINGS: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1ß receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification. SIGNIFICANCE: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Life Sci Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Life Sci Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos