PMID- 26514727
OWN - NLM
STAT- MEDLINE
DCOM- 20160315
LR  - 20220408
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 468
IP  - 1-2
DP  - 2015 Dec 4-11
TI  - Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF 
      rats.
PG  - 319-25
LID - S0006-291X(15)30805-6 [pii]
LID - 10.1016/j.bbrc.2015.10.105 [doi]
AB  - 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). METHODS AND 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-1beta 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Liu, Penghao
AU  - Liu P
AD  - 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.
FAU - Xie, Qihai
AU  - Xie Q
AD  - Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai, 
      China.
FAU - Wei, Tong
AU  - Wei T
AD  - 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.
FAU - Chen, Yichen
AU  - Chen Y
AD  - Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Chen, Hong
AU  - Chen H
AD  - Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China. Electronic address: hchen100@shsmu.edu.cn.
FAU - Shen, Weili
AU  - Shen W
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151026
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carrier Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
SB  - IM
MH  - Animals
MH  - Aorta/immunology/*pathology
MH  - Carrier Proteins/*immunology
MH  - Endothelium, Vascular/immunology/*pathology
MH  - Inflammasomes/*immunology
MH  - Male
MH  - Mitochondria/immunology/pathology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Obesity/*complications/*immunology/pathology
MH  - Rats, Inbred OLETF
MH  - Rats, Long-Evans
OTO - NOTNLM
OT  - Endothelial dysfunction
OT  - NLRP3
OT  - OLETF
OT  - Obesity
OT  - Vessel inflammation
EDAT- 2015/10/31 06:00
MHDA- 2016/03/16 06:00
CRDT- 2015/10/31 06:00
PHST- 2015/10/18 00:00 [received]
PHST- 2015/10/20 00:00 [accepted]
PHST- 2015/10/31 06:00 [entrez]
PHST- 2015/10/31 06:00 [pubmed]
PHST- 2016/03/16 06:00 [medline]
AID - S0006-291X(15)30805-6 [pii]
AID - 10.1016/j.bbrc.2015.10.105 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):319-25. doi: 
      10.1016/j.bbrc.2015.10.105. Epub 2015 Oct 26.