血管内皮细胞发育及分子机制

Vascular endothelial cell development and underlying mechanisms

心血管系统是胚胎发育中最先形成的器官之一,为机体提供营养成分和氧气。血管发育包括两部分,一是内皮祖细胞(Angioblast)聚集形成血管原基(Vasculogenesis),二是从已有血管形成新的血管分支(Angiogenesis)。此后由初级内皮细胞管召集平滑肌细胞形成功能性血管(Vessel maturation)。内皮祖细胞起源途径包括:由Flk1阳性中胚层细胞到成血成血管细胞(Hemangioblast)到血管内皮祖细胞;或由Flk1阳性中胚层细胞直接到血管内皮祖细胞。Flk1阳性中胚层细胞受到vegf、flk1、cloche、lycat、etsrp等关键基因或信号通路的调节,其中核心问题是原肠期中胚层如何形成Flk1阳性中胚层细胞及进一步分化成血管内皮祖细胞和成血血管细胞。文章集中评述内皮祖细胞发育、分化及其分子遗传调控机制,并展望本领域未来发展方向。

The cardiovascular system is one of the first organs formed during embryogenesis. Vessel development involves generating primary vascular endothelial tubes by aggregation of angioblasts （vasculogenesis）, creating a vascular network through endothelial sprouting （angiogenesis）, and pruning primary vascular tubes by recruiting smooth muscle cells to the vessel walls （vessel maturation）. Angioblast, the endothelial progenitor, is generated from hemangioblasts that are derived from the Flk1^＋ mesodermal cells, or directly from the Flk1^＋ mesodermal cells. Although several factors such as vega, flk1, cloche, lycat and estrp are essential for angioblast development, much of the signaling pathways underlying the derivation of angioblasts from the hemangioblasts or Flk1^＋ mesodermal cells remain unknown. This review will summarize our current knowledge, challenge, and future directions on molecular and cellular mechanisms of endothelial cell development.