Lin Yuankai, Jiang Weiya, Ng Jennifer, Jina Asmita, Wang Rong A
Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, California, USA.
Microcirculation. 2014 Oct;21(7):578-86. doi: 10.1111/micc.12135.
The 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.
We 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.
We 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.
Our data suggest that endothelial ephrin-B2 is required for endothelial-dependent arterial dilation and NO signaling in adult endothelium.
细胞表面蛋白 Ephrin-B2 在整个发育和成年期均表达于动脉内皮细胞而非静脉内皮细胞。内皮 Ephrin-B2 是血管发育和血管生成所必需的，但其在成熟动脉中的作用目前尚不清楚。我们研究了 Ephrin-B2 信号在成年内皮中的生理作用。
我们构建了成年条件性基因敲除小鼠，其内皮细胞中特异性缺失 Efnb2 基因，并通过活体显微镜评估提睾肌制备中对血流增加和乙酰胆碱（ACh）的血管舒张反应，以及通过体内超声评估颈动脉中的反应。
我们发现 Efnb2 条件性基因敲除小鼠在急性动脉舒张方面存在缺陷。提睾肌小动脉对血流增加或 ACh 的舒张反应受损，颈动脉对血流增加的舒张反应也受损。ACh 刺激后，突变动脉中一氧化氮（NO）的效应分子环磷酸鸟苷（cGMP）水平降低。血管舒张剂 NO 的供体 GSNO 减轻了突变体中的血管舒张缺陷。免疫染色显示，一部分 Ephrin-B2 蛋白与小窝蛋白-1（eNOS 的负调节因子）共定位。
我们的数据表明，内皮 Ephrin-B2 是成年内皮中内皮依赖性动脉舒张和 NO 信号传导所必需的。
