Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes
Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes
复制标题
吴茱萸碱逆转单核细胞中氧化低密度脂蛋白诱导的连接蛋白表达模式改变
DOI：
10.1097/fjc.0000000000000372
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发表时间：
2016-06-01
影响因子：
3
通讯作者：
Luo, Dan
中科院分区：
文献类型：
--
作者：
Liu, Yong;Fu, Yan-Qi;Luo, Dan
翻译后摘要：单核细胞粘附到血管内皮细胞是至关重要的动脉粥样硬化的发展。连接蛋白（Cxs）形成半通道或间隙连接，调节单核细胞-内皮细胞相互作用。我们以前发现，吴茱萸中的活性成分吴茱萸次碱，逆转了人脐静脉内皮细胞氧化低密度脂蛋白（ox-LDL）诱导的Cx表达的改变，从而降低了内皮细胞对单核细胞的粘附特性。本研究进一步研究了吴茱萸次碱对氧化低密度脂蛋白暴露的单核细胞中Cx表达的影响。在培养的人单核细胞系THP-1中，ox-LDL迅速降低了动脉粥样硬化保护性Cx 37的水平，但增强了致动脉粥样硬化性Cx43的水平，从而抑制了通过半通道释放的三磷酸腺苷。用吴茱萸次碱预处理恢复了Cx 37的表达，但抑制了ox-LDL诱导的Cx43的上调，从而提高了三磷酸腺苷依赖的半通道活性，并阻止了单核细胞粘附。这些作用的吴茱萸次碱衰减辣椒平，瞬时受体电位香草酸亚型1的拮抗剂。半通道阻断剂18 -GA也可减弱吴茱萸次碱的抗粘附作用。这项研究提供了额外的证据，表明芸香苷可以通过单核细胞中瞬时受体电位香草素亚型1的激活来调节Cx表达，这有助于芸香苷的抗粘附特性。
Abstract: Adhesion of monocytes to the vascular endothelium is crucial in atherosclerosis development. Connexins (Cxs) which form hemichannels or gap junctions, modulate monocyte-endothelium interaction. We previously found that rutaecarpine, an active ingredient of the Chinese herbal medicine Evodia, reversed the altered Cx expression induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells, and consequently decreases the adhesive properties of endothelial cells to monocytes. This study further investigated the effect of rutaecarpine on Cx expression in monocytes exposed to ox-LDL. In cultured human monocytic cell line THP-1, ox-LDL rapidly reduced the level of atheroprotective Cx37 but enhanced that of atherogenic Cx43, thereby inhibiting adenosine triphosphate release through hemichannels. Pretreatment with rutaecarpine recovered the expression of Cx37 but inhibited the upregulation of Cx43 induced by ox-LDL, thereby improving adenosine triphosphate-dependent hemichannel activity and preventing monocyte adhesion. These effects of rutaecarpine were attenuated by capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. The antiadhesive effects of rutaecarpine were also attenuated by hemichannel blocker 18&agr;-GA. This study provides additional evidence that rutaecarpine can modulate Cx expression through transient receptor potential vanilloid subtype 1 activation in monocytes, which contributes to the antiadhesive properties of rutaecarpine.