Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization
Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization
复制标题
DOI：
10.1016/j.lfs.2005.08.031
复制
发表时间：
2006-03-13
期刊：
影响因子：
6.1
通讯作者：
Wang, H
中科院分区：
文献类型：
--
作者：
Li, XW;Wang, H
α 7烟碱乙酰胆碱受体（α 7 nAChR）广泛表达于中枢和外周神经系统，也存在于多种非神经组织，如内皮细胞、支气管上皮细胞、皮肤角质形成细胞和血管平滑肌细胞。最近的证据表明，α 7 nAChR参与血管生成。在这里，我们研究了α 7 nAChR用于缺血性心脏病血运重建的可行性。采用RT-PCR和免疫组化方法检测人脐静脉内皮细胞（HUVECs）α 7 nAChR的表达。采用MTT法、荧光共聚焦显微镜和血管生成实验检测细胞功能。用免疫组织化学方法观察了大鼠心肌梗塞（MI）模型心肌毛细血管密度的变化。结果表明，α 7 nAChR激动剂胆碱可增加内皮细胞α 7 nAChR mRNA和蛋白的表达，增加细胞内Ca ~（2+）浓度，促进内皮细胞增殖和管腔形成。通过使用α 7 nAChR拮抗剂α-BTX观察到逆转作用。此外，在大鼠MI模型中，α 7 nAChR激动剂可增加缺血组织毛细血管密度，而拮抗剂美加明和α-BTX则抑制这种作用。我们的研究结果表明，α 7 nAChR参与调节EC的细胞功能和MI的毛细血管形成，这是血管生成的重要步骤。因此，内皮细胞上的α 7 nAChR可能是缺血性心脏病治疗性血管生成中血管重建的新内皮靶点。(c)2005年爱思唯尔公司All rights reserved.
Alpha 7 nicotinic acetylcholine receptor (0 nAChR) is widely expressed in the central and peripheral nervous systems, and is also found in several non-neuronal tissues, such as endothelial cells (ECs), bronchial epithelial cells, skin keratinocytes and vascular smooth muscle cells. Recent evidence suggests that alpha 7 nAChR is involved in angiogenesis. Here, we investigated the feasibility of alpha 7 nAChR for revascularization in ischemic heart disease. RT-PCR and immunohistochemistry were used to examine the expression of alpha 7 nAChR in human umbilical vein endothelial cell (HUVECs). The cellular function was examined using MTT, fluorescence confocal microscopy and angiogenesis assay in vitro. The capillary density in the rat model of myocardial infarction (MI) was investigated using immunohistochemistry. The results showed that alpha 7 nAChR agonists choline increased the expression of alpha 7 nAChR mRNA and protein, the intracellular Ca2+ concentration, proliferation and tube formation of ECs. Reverse effects were observed by using alpha 7 nAChR antagonist alpha-BTX. Furthermore, in the rat model of MI, alpha 7 nAChR agonist enhanced the capillary density in ischemic tissues, whereas antagonist mecamylamine and alpha-BTX inhibited the effect. Our results suggest that alpha 7 nAChR is involved in the regulation of cellular function in ECs, and capillary formation in MI, which are the important steps of angiogenesis. Therefore, alpha 7 nAChR on ECs may be a new endothelium target for revascularization in therapeutic angiogenesis of ischemic heart disease. (c) 2005 Elsevier Inc. All rights reserved.