Bone Morphogenetic Proteins in Vascular Homeostasis and Disease
- 1Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- 2VIB Center for the Biology of Disease, 3000 Leuven, Belgium
- 3KU Leuven Department of Human Genetics, 3000 Leuven, Belgium
- 4Cancer Genomics Centre Netherlands, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- 5Institut National de la Santé et de la Recherche Mécale (INSERM), U1036, 38000 Grenoble, France
- 6Laboratoire Biologie du Cancer et de l'Infection, Commissariat à l'Énergie Atomique et aux Energies Alternatives, Biosciences and Biotechnology Institute of Grenoble, 38000 Grenoble, France
- 7University of Grenoble Alpes, 38000 Grenoble, France
- Correspondence: m.j.t.h.goumans{at}lumc.nl; sabine.bailly{at}cea.fr
Abstract
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.
