title: Silence of NLRP3 suppresses atherosclerosis and stabilizes plaques in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis.
  
  
  METHODS
  Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR.
  
  
  RESULTS
  Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques.
  
  
  CONCLUSIONS
  NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation.
authors.affiliation: Department of Cardiology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Cardiology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China.
authors.forename: Zushun
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.affiliation: Department of Cardiology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China.
authors.forename: Qichong
authors.initials: Q
authors.lastname: Xing
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse