From the Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA; and Departments of Pediatrics and Pathology, University of Washington, Seattle.
Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):e17-e24. doi: 10.1161/ATVBAHA.118.310223.
The vascular system forms as a branching network of endothelial cells that acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial specification depends on gene targets transcribed by Ets domain-containing factors, including Ets variant gene 2 (Etv2), together with the activity of chromatin-remodeling complexes containing Brahma-related gene-1 (Brg1). Once specified and assembled into vessels, mechanisms regulating lumen diameter and axial growth ensure that the structure of the branching vascular network matches the need for perfusion of target tissues. In addition, blood vessels provide important morphogenic cues that guide or direct the development of organs forming around them. As the embryo grows and lumen diameters increase, smooth muscle cells wrap around the nascent vessel walls to provide mechanical strength and vasomotor control of the circulation. Increasing mechanical stretch and wall strain promote smooth muscle cell differentiation via coupling of actin cytoskeletal remodeling to myocardin and serum response factor-dependent transcription. Remodeling of artery walls by developmental signaling pathways reappears in postnatal blood vessels during physiological and pathological adaptation to vessel wall injury, inflammation, or chronic hypoxia. Recent reports providing insights into major steps in vascular development are reviewed here with a particular emphasis on studies that have been recently published in
脉管系统形成具有分支网络的内皮细胞，这些细胞获得动脉、静脉、造血或淋巴的特性。内皮细胞的特化取决于 Ets 结构域包含因子转录的基因靶标，包括 Ets 变体基因 2（Etv2），以及包含 Brg1 的染色质重塑复合物的活性。一旦被指定并组装成血管，调节管腔直径和轴向生长的机制确保分支血管网络的结构与灌注靶组织的需求相匹配。此外，血管提供了重要的形态发生线索，指导或引导围绕它们形成的器官的发育。随着胚胎的生长和管腔直径的增加，平滑肌细胞围绕新生的血管壁缠绕，为循环提供机械强度和血管舒缩控制。增加的机械拉伸和壁应变通过肌动蛋白细胞骨架重塑与肌球蛋白和血清反应因子依赖性转录的偶联，促进平滑肌细胞分化。发育信号通路对动脉壁的重塑在出生后血管中再次出现，以适应血管壁损伤、炎症或慢性缺氧的生理和病理变化。本文回顾了血管发育的主要步骤的最新研究报告，特别强调了最近发表的研究。
