TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.
TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.
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TRPV1介导的UCP2上调可改善高血糖诱导的内皮功能障碍
DOI：
10.1186/1475-2840-12-69
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发表时间：
2013-04-22
影响因子：
9.3
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Sun J;Pu Y;Wang P;Chen S;Zhao Y;Liu C;Shang Q;Zhu Z;Liu D
背景糖尿病心血管并发症的特点是氧化应激诱导的内皮功能障碍。解偶联蛋白2（UCP 2）是线粒体活性氧（ROS）产生的调节因子，可以拮抗氧化应激，但增强UCP 2活性以抑制ROS的方法很少。我们以前的研究表明，辣椒素激活瞬时受体电位香草酸1（TRPV 1）可以预防心脏代谢紊乱。在这项研究中，我们进行了实验，在体外和体内研究辣椒素治疗对内皮UCP 2和氧化应激的影响。我们假设辣椒素激活TRPV 1通过UCP 2介导的抗氧化作用减轻高血糖诱导的内皮功能障碍。方法TRPV 1-/-，UCP 2-/-和db/db小鼠，以及匹配的野生型（WT）对照小鼠，被纳入本研究。一些小鼠接受饮食辣椒素14周。培养小鼠动脉和内皮细胞。内皮功能进行了检查，免疫组织化学和分子分析performed.ResultsUnder高糖条件下，TRPV 1的表达和蛋白激酶A（PKA）的磷酸化被发现在培养的内皮细胞减少，和高糖对这些分子的影响逆转辣椒素的管理。此外，高糖暴露增加ROS的产生和减少一氧化氮（NO）水平在内皮细胞和动脉中，分别通过二氢乙锭（DHE）和β-2 DA荧光评价。辣椒素给药减少了ROS的产生，通过激活TRPV 1恢复高糖诱导的内皮功能障碍，并在体内以UCP 2依赖的方式起作用。饮食辣椒素管理14周增加PKA磷酸化水平和UCP 2表达，改善血管氧化应激和增加NO水平观察糖尿病小鼠。长期饮食给予辣椒素促进糖尿病小鼠内皮依赖性舒张。结论辣椒素激活TRPV 1可能通过PKA/UCP 2通路对高糖诱导的血管内皮功能障碍具有保护作用。
BackgroundDiabetic cardiovascular complications are characterised by oxidative stress-induced endothelial dysfunction. Uncoupling protein 2 (UCP2) is a regulator of mitochondrial reactive oxygen species (ROS) generation and can antagonise oxidative stress, but approaches that enhance the activity of UCP2 to inhibit ROS are scarce. Our previous studies show that activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin can prevent cardiometabolic disorders. In this study, we conducted experiments in vitro and in vivo to investigate the effect of capsaicin treatment on endothelial UCP2 and oxidative stress. We hypothesised that TRPV1 activation by capsaicin attenuates hyperglycemia-induced endothelial dysfunction through a UCP2-mediated antioxidant effect.MethodsTRPV1-/-, UCP2-/-and db/db mice, as well as matched wild type (WT) control mice, were included in this study. Some mice were subjected to dietary capsaicin for 14 weeks. Arteries isolated from mice and endothelial cells were cultured. Endothelial function was examined, and immunohistological and molecular analyses were performed.ResultsUnder high-glucose conditions, TRPV1 expression and protein kinase A (PKA) phosphorylation were found to be decreased in the cultured endothelial cells, and the effects of high-glucose on these molecules were reversed by the administration of capsaicin. Furthermore, high-glucose exposure increased ROS production and reduced nitric oxide (NO) levels both in endothelial cells and in arteries that were evaluated respectively by dihydroethidium (DHE) and DAF-2 DA fluorescence. Capsaicin administration decreased the production of ROS, restored high-glucose-induced endothelial dysfunction through the activation of TRPV1 and acted in a UCP2-dependent manner in vivo. Administration of dietary capsaicin for 14 weeks increased the levels of PKA phosphorylation and UCP2 expression, ameliorated the vascular oxidative stress and increased NO levels observed in diabetic mice. Prolonged dietary administration of capsaicin promoted endothelium-dependent relaxation in diabetic mice. However, the beneficial effect of capsaicin on vasorelaxation was absent in the aortas of UCP2-/-mice exposed to high-glucose levels.ConclusionTRPV1 activation by capsaicin might protect against hyperglycemia-induced endothelial dysfunction through a mechanism involving the PKA/UCP2 pathway.
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DOI：
10.1016/j.bbrc.2004.06.149
发表时间：
2004-08-11
影响因子：
3.1
作者：
Akiba, Y;Kato, S;Hibi, T
通讯作者：
Hibi, T
影响因子：
20.1
作者：
Chan, Samuel H. H.;Wu, Chiung-Ai;Chan, Julie Y. H.
通讯作者：
Chan, Julie Y. H.
影响因子：
6.6
作者：
Chu, Kwan Yi;Leung, Po Sing
通讯作者：
Leung, Po Sing
影响因子：
8.2
作者：
Dong, Y. F.;Liu, L.;Kim-Mitsuyama, S.
通讯作者：
Kim-Mitsuyama, S.
影响因子：
7.2
作者：
Lee, Mak-Soon;Kim, Chong-Tai;Kim, Yangha
通讯作者：
Kim, Yangha