Bone Morphogenetic Proteins in Vascular Homeostasis and Disease

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.