TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway
TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway
复制标题
TRPV1 激动剂通过激活 eNOS/NO 通路抑制内皮细胞炎症
DOI：
10.1016/j.atherosclerosis.2017.03.016
复制
发表时间：
2017-05-01
期刊：
影响因子：
5.3
通讯作者：
Zhu, Mingjun
中科院分区：
文献类型：
--
作者：
Wang, Youping;Cui, Lin;Zhu, Mingjun
背景和目的：瞬时受体电位香草样蛋白1型通道（TRPV1）在内皮细胞（ECs）中表达并激活内皮型一氧化氮合酶（eNOS）。最近的研究暗示TRPV1在减轻炎症反应。然而，其有益作用的机制尚不清楚。在本研究中，我们研究了TRPV1是否通过eNOS/NO途径抑制ECs的炎症反应。方法：在脂多糖（LPS）刺激前，用辣椒素（CAP，一种特异性TRPV1激动剂）培养人脐静脉内皮细胞（HUVECs）和肾微血管内皮细胞（MVECs），同时加入或不加入TRPV1、NOS或Ca2+依赖性磷脂肌醇3-激酶(PI3K)/Akt通路的特异性抑制剂。分别采用Griess法和基于免疫分析的多重分析法评估NO代谢物、蛋白表达和炎症分子。单核细胞粘附通过测量附着在lps刺激的内皮细胞上的荧光标记的人单核细胞来测定。结果：在HUVECs中，CAP处理增加了NO的产生，并且CAP诱导的NO产生伴随着eNOS（ser1177）磷酸化的增加。此外，CAP还能减弱lps诱导的细胞因子和趋化因子的产生、粘附分子的表达、NF-kappa B的激活和HUVECs中单核细胞的粘附，而这些作用通过抑制TRPV1、NOS或Ca2+依赖性PI3K/Akt通路而被消除。此外，在doca盐高血压小鼠肾mvec中也观察到TRPV1的这些保护作用。结论：TRPV1激活通过激活Ca2+/PI3K/Akt/eNOS/NO通路抑制ECs的炎症反应，在盐敏感高血压小鼠的ECs中也有保护作用。(C) 2017由爱思唯尔爱尔兰有限公司出版。
Background and aims: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway.Methods: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca2+-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation. NO metabolites, protein expression, and inflammatory molecules were evaluated by Griess assay and immune assay-based multiplex analysis, respectively. Monocyte adhesion was determined by measuring the fluorescently labeled human monocytes attached to LPS-stimulated ECs.Results: In HUVECs, treatment with CAP increased NO production, and CAP-induced NO production was accompanied by increased eNOS(ser1177) phosphorylation. Additionally, CAP attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression, activation of NF-kappa B, and monocyte adhesion in HUVECs, and these effects were abrogated by the inhibition of TRPV1, NOS, or Ca2+-dependent PI3K/Akt pathway. Moreover, these protective actions of TRPV1 were also observed in renal MVECs isolated from DOCA-salt hypertensive mice.Conclusions: Our results indicate that TRPV1 activation suppresses the inflammatory response of ECs via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway, the protective effects are also documented in ECs derived from salt-sensitive hypertensive mice. (C) 2017 Published by Elsevier Ireland Ltd.