Bone morphogenetic protein and blood vessels: new insights into endothelial cell junction regulation.

Abstract

BMP signaling is an important regulator of vascular development and homeostasis, and perturbations of BMP pathway components are linked to vascular disease. However, until recently BMP's broad requirements in many developmental programs delayed cause-and-effect and mechanistic studies of its vascular role in vivo. This review covers recent findings that illuminate the role of BMP signaling in endothelial cells of blood vessels, and highlights effects of BMP signaling on endothelial cell junctions and vascular barrier function. BMP signaling in endothelial cells of blood vessels is context-dependent, and can either be pro-angiogenic and promote vascular sprouting, or antiangiogenic and promote vascular homeostasis. I discuss how distinct BMP signaling inputs impact blood vessel formation and function, with emphasis on new studies that investigate how BMP signaling affects endothelial cell junctions and vascular permeability. BMP signaling is important but complex in endothelial cells of blood vessels, with multiple distinct inputs leading to opposing cellular behaviors and phenotypic outputs in ways that are poorly understood. Endothelial cell-cell junctions are a target of BMP signaling, and junction stability can be tuned in either direction by BMP inputs. Several human diseases have perturbed junctions linked to BMP signaling changes.