The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function

Blood vessels expand via sprouting angiogenesis, and this process involves numerous endothelial cell behaviors, such as collective migration, proliferation, cell–cell junction rearrangements, and anastomosis and lumen formation. Subsequently, blood vessels remodel to form a hierarchical network that circulates blood and delivers oxygen and nutrients to tissue. During this time, endothelial cells become quiescent and form a barrier between blood and tissues that regulates transport of liquids and solutes. Bone morphogenetic protein (BMP) signaling regulates both proangiogenic and homeostatic endothelial cell behaviors as blood vessels form and mature. Almost 30 years ago, human pedigrees linked BMP signaling to diseases associated with blood vessel hemorrhage and shunts, and recent work greatly expanded our knowledge of the players and the effects of vascular BMP signaling. Despite these gains, there remain paradoxes and questions, especially with respect to how and where the different and opposing BMP signaling outputs are regulated. This review examines endothelial cell BMP signaling in vitro and in vivo and discusses the paradox of BMP signals that both destabilize and stabilize endothelial cell behaviors.