Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth.
Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth.
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DOI：
10.1007/s10456-016-9498-5
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发表时间：
2016-04
期刊：
影响因子：
9.8
通讯作者：
Cleaver O
中科院分区：
文献类型：
--
作者：
Koo Y;Barry DM;Xu K;Tanigaki K;Davis GE;Mineo C;Cleaver O
心血管功能依赖于内皮细胞（ECs）形成通畅、连续和稳定的血管。血管发育由血管发生启动，因为EC聚结成线性聚集体并组织形成允许血液流动的中央管腔。体内血管“小管形成”的分子机制才刚刚开始被解开。我们先前表明，GTP酶相互作用蛋白Rasip 1是早期胚胎连续血管腔形成所必需的。Rasip 1 −/− EC表现出适当的细胞极性和细胞形状的丧失，EC-EC连接的破坏定位以及EC与细胞外基质（ECM）粘附的缺陷。体外研究表明，培养的EC中的Rasip 1缺失阻断了小管形成。Rasip 1在血管最初形成后是否需要仍不清楚。在这里，我们表明，Rasip 1是必不可少的胚胎血管的形成和维护，但不是在静止的成人血管。在三种血管生长模型中，Rasip 1也是血管生成所必需的：体外基质侵袭、视网膜血管生长和定向体内血管生成试验（DIVAA）。因此，Rasip 1在胚胎血管生长、出生后血管生成萌芽和重塑中是必需的，但对于维持已建立的血管是必需的，使其成为潜在的抗血管生成治疗靶点。
Cardiovascular function depends on patent, continuous and stable blood vessel formation by endothelial cells (ECs). Blood vessel development initiates by vasculogenesis, as ECs coalesce into linear aggregates and organize to form central lumens that allow blood flow. Molecular mechanisms underlying in vivo vascular ‘tubulogenesis’ are only beginning to be unraveled. We previously showed that the GTPase-interacting protein called Rasip1 is required for the formation of continuous vascular lumens in the early embryo. Rasip1−/− ECs exhibit loss of proper cell polarity and cell shape, disrupted localization of EC-EC junctions and defects in adhesion of ECs to extracellular matrix (ECM). In vitro studies showed that Rasip1 depletion in cultured ECs blocked tubulogenesis. Whether Rasip1 is required in blood vessels after their initial formation remained unclear. Here, we show that Rasip1 is essential for vessel formation and maintenance in the embryo, but not in quiescent adult vessels. Rasip1 is also required for angiogenesis in three models of blood vessel growth: in vitro matrix invasion, retinal blood vessel growth and Directed In vivo Angiogenesis Assays (DIVAA). Rasip1 is thus necessary in growing embryonic blood vessels, postnatal angiogenic sprouting and remodeling, but is dispensable for maintenance of established blood vessels, making it a potential anti-angiogenic therapeutic target.