title: Nalp3 inflammasome is activated and required for vascular smooth muscle cell calcification.
abstract: BACKGROUND
  The calcification of blood vessels correlates with increased morbidity and mortality in patients with atherosclerosis, diabetes, and end-stage kidney disease. Increased inflammasome activation has been shown to play an important role in the pathogenesis of atherosclerosis. However, the contribution of inflammasome activation on the development of vascular calcification has not been investigated.
  
  
  METHODS
  β-Glycerophosphate (β-GP) was used as a procedure to induce extensive artery calcification in primary vascular smooth muscle cells (VSMCs). Analysis of the levels of Nalp3 inflammasome complex was performed by quantitative real-time PCR and western blotting. The effect of Nalp3 deficiency on VSMC calcification was examined after transfecting Nalp3 siRNA into cultured VSMCs.
  
  
  RESULTS
  We demonstrated for the first time that the mRNA levels of Nalp3 inflammasome complex including Nalp3, ASC and caspase1 were upregulated in calcifying VSMCs, resulting in increased IL-1β secretion. Inhibition of inflammasome activation by Nalp3 RNA interference reduced IL-1β secretion and inhibited VSMC calcification. Further analysis of clinical popliteal artery specimens showed an upregulation of inflammasome complex mRNA levels (4/5) and caspase1 activity (5/5) compared with their non-calcified adjacent tissues, indicating that Nalp3 inflammasome was tightly correlated with arterial calcification disease.
  
  
  CONCLUSIONS
  Our findings indicate that activation of the Nalp3-mediated inflammatory response pathway is an important venue associated with host response and pathogenesis of VSMC calcification.
authors: Hainan Branch of Chinese PLA General Hospital Sanya city, Hainan 572000, China; Beijing Institute of Biotechnology, Beijing 100850, China.
authors: Chaoyang
authors: C
authors: Wen
authors: Xiaoli
authors: X
authors: Yang
authors: Zhifeng
authors: Z
authors: Yan
authors: Man
authors: M
authors: Zhao
authors: Xiang
authors: X
authors: Yue
authors: Xiaozhong
authors: X
authors: Cheng
authors: Zirui
authors: Z
authors: Zheng
authors: Kai
authors: K
authors: Guan
authors: Jianping
authors: J
authors: Dou
authors: Tao
authors: T
authors: Xu
authors: Yanhong
authors: Y
authors: Zhang
authors: Ting
authors: T
authors: Song
authors: Congwen
authors: C
authors: Wei
authors: Hui
authors: H
authors: Zhong
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D058847:Inflammasomes / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D061205:Vascular Calcification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D012313:RNA
keywords: IL-1β secretion; Nalp3 inflammasomes; VSMC calcification; VSMCs; vascular smooth muscle cells; β-GP; β-glycerophosphate