Role of connexin37 and connexin40 in vascular development.
Role of connexin37 and connexin40 in vascular development.
复制标题
connexin37 和 connexin40 在血管发育中的作用。
DOI：
10.1080/cac.10.4-6.379.385
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发表时间：
2003
影响因子：
--
通讯作者：
McWhorter,AndreaR
中科院分区：
文献类型：
--
作者：
Simon,AlexanderM;McWhorter,AndreaR
缺乏连接蛋白37（Cx 37）和连接蛋白40（Cx40）的小鼠，血管内皮细胞中表达的间隙连接蛋白，围产期死亡，明显的血管异常。早期血管发生正常进行，但到E18.5 Cx 37-/-Cx40-/-动物表现出血管扩张和充血以及皮肤、睾丸、肠道和肺部局部出血。睾丸中存在异常的血管通道，常形成海绵状血管瘤样缺损。肠粘膜下层和固有层中也有异常大而扩张的血管。Cx40的消融对内皮染料转移的影响大于Cx 37的消融，并且Cx40消融的影响具有年龄依赖性。只有在缺乏Cx 37和Cx40的胚胎性动脉瘤中，内皮偶联才完全丧失。令人惊讶的是，Cx40的消除导致免疫印迹上主动脉内皮Cx 37的大幅下降，并且Cx 37的缺失也降低内皮Cx40水平。相反，在中间层，Cx 37和Cx43增加时，Cx40被消融。这些研究表明，Cx 37和Cx40是共同的内皮通讯的关键，并提供了一个重要的作用，在血管发育的间隙连接的证据。此外，Cx 37和Cx40在血管内皮中的正常表达似乎相互依赖。
Mice lacking both connexin37 (Cx37) and connexin40 (Cx40), gap junction proteins expressed in vascular endothelium, die perinatally with pronounced vascular abnormalities. Early vasculogenesis proceeds normally, but by E18.5 Cx37−/−Cx40−/−animals display vessel dilatation and congestion as well as localized hemorrhages in skin, testis, intestines, and lungs. Abnormal vascular channels are present in the testis, often forming cavernous hemangioma-like defects. Unusually large, distended vessels are also present in the submucosa and lamina propria of the intestine. Ablation of Cx40 has a greater effect on endothelial dye-transfer than ablation of Cx37, and the effect of Cx40 ablation is age-dependent. Only in embryonic aortas lacking both Cx37 and Cx40 is there a complete loss of endothelial coupling. Surprisingly, elimination of Cx40 results in a large drop in aortic endothelial Cx37 on western blots, and deletion of Cx37 also reduces endothelial Cx40 levels. In contrast, in the medial layer, both Cx37 and Cx43 increase when Cx40 is ablated. These studies indicate that Cx37 and Cx40 are collectively critical for endothelial communication and provide evidence of an important role for gap junctions in vascular development. In addition, Cx37 and Cx40 appear to be mutually dependent on each other for normal expression in vascular endothelium.