Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats
Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats
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NLRP3 炎性体的激活诱导肥胖 OLETF 大鼠血管功能障碍
DOI：
10.1016/j.bbrc.2015.10.105
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发表时间：
2015-12-04
影响因子：
3.1
通讯作者：
Shen, Weili
中科院分区：
文献类型：
--
作者：
Liu, Penghao;Xie, Qihai;Shen, Weili
目的：肥胖引起的血管功能障碍与慢性低度全身炎症有关。最近的研究表明，NLRP3是由NOD样受体(NLR)家族成员形成的多蛋白复合体，是介导体内不孕症炎症的关键成分，但在肥胖相关血管功能障碍中的作用尚不清楚。在本研究中，我们探讨NLRP3的激活是否与肥胖的大冢长伊文斯德岛肥胖大鼠(OLETF)的血管炎症有关。方法和结果：研究了3月龄和12月龄的雄性Long-Evans德岛肥胖大鼠(LETO)的血管炎症反应。与年龄匹配的LETO对照组相比，肥胖OLETF患者对乙酰胆碱反应的主动脉松弛功能随着年龄的增长而逐渐降低，肥胖OLETF患者早期和持续性内皮功能障碍。这些变化与主动脉内皮型一氧化氮合酶(ENOS)含量的平行变化、巨噬细胞聚集和内膜增厚有关。与LETO相比，OLETF大鼠NLRP3升高。与炎性小体激活一致，OLETF大鼠前天冬氨酸氨基转移酶-1向裂解和激活形式的转化以及IL-1β的表达显著增加。此外，我们观察到动力蛋白相关蛋白-1(Drp1)的表达增加，融合相关蛋白光学Atropy-1(OPA1)的表达降低。结论：肥胖可能通过激活NLRP3和线粒体功能障碍来加速OLETFS的内皮功能障碍。(C)2015 Elsevier Inc.保留所有权利。
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-1 beta 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. (C) 2015 Elsevier Inc. All rights reserved.