McAllister Heart Institute, University of North Carolina at Chapel Hill, USA.
Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2216-22. doi: 10.1161/ATVBAHA.111.230235. Epub 2011 Jul 7.
Bone morphogenetic proteins (BMPs) are potently proangiogenic; however, the mechanisms underlying the regulation of vessel development by BMPs are not fully understood. To assess the significance of BMP endothelial cell precursor-derived regulator (BMPER) in blood vessel formation in vivo, we investigated its role in retinal angiogenesis.
In a model of oxygen-induced retinopathy, Bmper mRNA expression and protein levels are downregulated, correlating with the initiation of Sma and Mad related protein phosphorylation in endothelial cells. Moreover, Bmper haploinsufficiency results in an increased rate of retinal revascularization, with retinas from Bmper+/- mice displaying increased numbers of branching points and angiogenic sprouts at the leading edge of the newly formed vasculature. Furthermore, although Bmper haploinsufficiency does not alter Bmp expression, it does lead to an increase in BMP signaling, as evidenced by increased phosphorylated Sma and Mad related protein levels in endothelial cells and increased expression of known BMP target genes.
These observations provide compelling evidence that BMPER is important in the regulation of BMP signaling and revascularization in the hypoxic retina. These bring forth the possibility of novel therapeutic approaches for pathological angiogenesis based on manipulation of BMP signaling.
骨形态发生蛋白（BMPs）具有很强的促血管生成作用；然而，BMPs 调节血管发育的机制尚未完全阐明。为了评估 BMP 内皮细胞前体衍生调节剂（BMPER）在体内血管形成中的意义，我们研究了其在视网膜血管生成中的作用。
在氧诱导的视网膜病变模型中，Bmper mRNA 表达和蛋白水平下调，与内皮细胞中 Smad 和 Mad 相关蛋白磷酸化的启动相关。此外，Bmper 杂合不足导致视网膜再血管化率增加，Bmper+/- 小鼠的视网膜在新形成的血管前缘显示出更多的分支点和血管生成芽。此外，尽管 Bmper 杂合不足不改变 Bmp 的表达，但确实导致 BMP 信号的增加，这表现在内皮细胞中磷酸化的 Smad 和 Mad 相关蛋白水平增加以及已知的 BMP 靶基因的表达增加。
这些观察结果提供了令人信服的证据，表明 BMPER 在缺氧视网膜中 BMP 信号转导和再血管化的调节中具有重要作用。这些为基于 BMP 信号转导的病理性血管生成的新治疗方法提供了可能性。
