title: Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats.
abstract: OBJECTIVE
  Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF).
  
  
  RESULTS
  Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas.
  
  
  CONCLUSIONS
  These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Penghao
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai, China.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: hchen100@shsmu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: wlshen@sibs.ac.cn.
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology*; D002352:Carrier Proteins / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D058847:Inflammasomes / Q000276:immunology*; D008297:Male; D008928:Mitochondria / Q000276:immunology / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat
keywords: Endothelial dysfunction; NLRP3; OLETF; Obesity; Vessel inflammation