Identifying the factors that regulate vasculogenesis and angiogenesis is of key therapeutic importance, as dysregulation of these processes can contribute to many types of human disease. Bone morphogenetic proteins (BMPs), which are members of the TGFβ protein family, are known to be involved in the development and homeostasis of vascular systems. On page , Tetsuro Watabe and colleagues (p. ) uncover a specific role for BMP-9 in promoting endothelial-cell proliferation. In contrast to previously published findings that suggest an inhibitory role for BMP-9, they show here using various approaches that this factor promotes vasculogenesis and angiogenesis ex vivo and in vivo. Furthermore, addition of exogenous BMP-9 increases the number of endothelial cells obtained when VEGFR2+ progenitor cells are differentiated in vitro. siRNA knockdown and overexpression studies show that this increase in endothelial-cell yield is mediated by BMP-9-mediated activation of activin-receptor-like kinase 1 (ALK-1), which is known to be preferentially expressed by endothelial cells. BMP-9–ALK-1 signalling activates downstream VEGF-VEGFR2 and Ang-1–Tie2 pathways, both of which are known to contribute to angiogenesis. These data increase our understanding of how BMPs influence vasculogenesis and angiogenesis, and suggest that BMP-9 is a therapeutic target for diseases in which these processes are dysregulated.
