Endothelial Ephrin-B2 is Essential for Arterial Vasodilation in Mice
Endothelial Ephrin-B2 is Essential for Arterial Vasodilation in Mice
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DOI：
10.1111/micc.12135
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发表时间：
2014-10-01
期刊：
影响因子：
2.4
通讯作者：
Wang, Rong A.
中科院分区：
文献类型：
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作者：
Lin, Yuankai;Jiang, Weiya;Wang, Rong A.
目的细胞表面蛋白肝配蛋白-B2 在整个发育和成年期在动脉而不是静脉 EC 中表达。内皮肝配蛋白-B2 是血管发育和血管生成所必需的，但其在已建立的动脉中的作用目前尚不清楚。我们研究了肝配蛋白-B2信号在成人内皮细胞中的生理作用。方法我们生成了ECs中特异缺乏Efnb2基因的成年条件性敲除小鼠，并通过活体显微镜评估了提睾肌制剂中血流增加和ACh的血管舒张反应，并通过体内超声评估了颈动脉中的血管舒张反应。结果我们发现Efnb2条件性敲除小鼠在急性动脉扩张方面存在缺陷。提睾小动脉的血管舒张功能因流量增加或乙酰胆碱的增加而受损，而颈动脉的血管舒张则因流量增加而受损。乙酰胆碱刺激后，突变动脉中的 cGMP（NO 效应物）水平降低。 GSNO，血管舒张剂NO的供体，减轻了突变体的血管舒张缺陷。免疫染色显示，肝配蛋白-B2 蛋白的一个子集与 eNOS 负调节因子 Caveolin-1 共定位。结论我们的数据表明，内皮肝配蛋白-B2 是成人内皮细胞中内皮依赖性动脉扩张和 NO 信号传导所必需的。
ObjectiveThe cell surface protein ephrin-B2 is expressed in arterial and not venous ECs throughout development and adulthood. Endothelial ephrin-B2 is required for vascular development and angiogenesis, but its role in established arteries is currently unknown. We investigated the physiological role of ephrin-B2 signaling in adult endothelium.MethodsWe generated adult conditional knockout mice lacking the Efnb2 gene specifically in ECs and evaluated the vasodilation responses to blood flow increase and ACh in the cremaster muscle preparation by intravital microscope and in carotid artery by in vivo ultrasound.ResultsWe found that the Efnb2 conditional knockout mice were defective in acute arterial dilation. Vasodilation was impaired in cremaster arterioles in response to either increased flow or ACh, and in the carotid arteries in response to increased flow. Levels of cGMP, an effector of NO, were diminished in mutant arteries following ACh stimulation. GSNO, a donor for the vasodilator NO, alleviated the vasodilatory defects in the mutants. Immunostaining showed that a subset of ephrin-B2 proteins colocalized with caveolin-1, a negative regulator of eNOS.ConclusionsOur data suggest that endothelial ephrin-B2 is required for endothelial-dependent arterial dilation and NO signaling in adult endothelium.