Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
Cold Spring Harb Perspect Biol. 2018 Feb 1;10(2):a031989. doi: 10.1101/cshperspect.a031989.
It is well established that control of vascular morphogenesis and homeostasis is regulated by vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), Delta-like 4 (Dll4), angiopoietin, and ephrin signaling. It has become clear that signaling by bone morphogenetic proteins (BMPs), which have a long history of studies in bone and early heart development, are also essential for regulating vascular function. Indeed, mutations that cause deregulated BMP signaling are linked to two human vascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. These observations are corroborated by data obtained with vascular cells in cell culture and in mouse models. BMPs are required for normal endothelial cell differentiation and for venous/arterial and lymphatic specification. In adult life, BMP signaling orchestrates neo-angiogenesis as well as vascular inflammation, remodeling, and calcification responses to shear and oxidative stress. This review emphasizes the pivotal role of BMPs in the vascular system, based on studies of mouse models and human vascular disorders.
血管形态发生和稳态的控制是由血管内皮生长因子（VEGF）、成纤维细胞生长因子（FGF）、Delta-like 4（Dll4）、血管生成素和 Ephrin 信号调节的，这一点已得到充分证实。已经清楚的是，骨形态发生蛋白（BMPs）的信号传导对于调节血管功能也是必不可少的，BMPs 在骨骼和早期心脏发育方面的研究历史悠久。事实上，导致 BMP 信号传导失调的突变与两种人类血管疾病——遗传性出血性毛细血管扩张症和肺动脉高压有关。这些观察结果得到了血管细胞在细胞培养和小鼠模型中获得的数据的证实。BMPs 对于正常的内皮细胞分化以及静脉/动脉和淋巴特异性是必需的。在成年期，BMP 信号传导协调新血管生成以及血管炎症、重塑和对剪切和氧化应激的钙化反应。基于对小鼠模型和人类血管疾病的研究，本综述强调了 BMPs 在血管系统中的关键作用。
