Rutaecarpine prevented dysfunction of endothelial gap junction induced by Ox-LDL via activation of TRPV1
Rutaecarpine prevented dysfunction of endothelial gap junction induced by Ox-LDL via activation of TRPV1
复制标题
芸香碱通过激活 TRPV1 来预防 Ox-LDL 诱导的内皮间隙连接功能障碍。
DOI：
10.1016/j.ejphar.2015.02.051
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发表时间：
2015-06-05
影响因子：
5
通讯作者：
Luo, Dan
中科院分区：
文献类型：
--
作者：
Peng, Wei-Jie;Liu, Yong;Luo, Dan
由连接蛋白形成的间隙连接已被证明在动脉粥样硬化形成中发挥重要作用。据报道，芸香碱可抑制单核细胞迁移，这表明其具有抗动脉粥样硬化活性的潜力。本研究评估了吴茱萸碱对内皮功能障碍的影响，并重点研究了吴茱萸碱对内皮细胞连接蛋白表达的调节作用。通过将 HUVEC-12 暴露于 Ox-LDL (100 mg/l) 24 小时，诱导内皮损伤，这降低了保护性蛋白 Cx37 和 Cx40 的表达，但在 mRNA 和蛋白水平上诱导致动脉粥样硬化的 Cx43 表达，同时碘化丙啶通过间隙连接的扩散受损。吴茱萸碱预处理可有效恢复Cx37和Cx40的表达，但抑制Cx43的表达，从而改善间隙连接通讯并显着预防内皮功能障碍。因此，细胞活力和一氧化氮产量增加，乳酸脱氢酶产量减少，单核细胞粘附受到抑制。经辣椒西平预处理后，吴茱萸的这些保护作用显着减弱，辣椒西平是瞬时受体电位香草酸亚型 1 (TRPV1) 的竞争性拮抗剂。总之，本研究首次报道了吴茱萸碱在体外可预防 Ox-LDL 诱导的内皮损伤和间隙连接功能障碍，这与通过 TRPV1 激活调节连接蛋白表达模式有关。这些结果表明，吴茱萸碱具有作为具有新机制的抗动脉粥样硬化剂的潜力。 (C) 2015 Elsevier B.V. 保留所有权利。
Gap junctions, which is formed by connexins, has been proved to play an important role in the atherogenesis development. Rutaecarpine was reported to inhibited monocyte migration, which indicates its potential for anti-atherosclerosis activity. This study evaluated the effect of rutaecarpine on endothelial dysfunction, and focused on the regulation of connexin expression in endothelial cells by rutaecarpine. Endothelia damage was induced by exposing HUVEC-12 to Ox-LDL (100 mg/l) for 24 h, which decreased the expression of protective proteins Cx37 and Cx40, but induced atherogenic Cx43 expression, in both mRNA and protein levels, concomitant with the impaired propidium iodide diffusion through the gap junctions. Pretreatment with rutaecarpine effectively recovered the expression of Cx37 and Cx40, but inhibited Cx43 expression, thereby improving gap junction communication and significantly prevented the endothelial dysfunction. Consequently, the cell viability and nitric oxide production were increased, lactate dehydrogenase production was decreased and monocyte adhesion was inhibited. These protective effects of rutaecarpine were remarkably attenuated by pretreatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid subtype 1 (TRPV1). In summary, this study is the first to report that rutaecarpine prevents endothelial injury and gap junction dysfunction induced by Ox-LDL in vitro, which is related to regulation of connexin expression patterns via TRPV1 activation. These results suggest that rutaecarpine has the potential for use as an anti-atherosclerosis agent with a novel mechanism. (C) 2015 Elsevier B.V. All rights reserved.