Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling
Abstract
Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impaired signaling through bone morphogenetic protein (BMP) receptor complexes in endothelial cells. Although BMP-9 plays a central role in activating this pathway by binding to ALK1 and BMPR-II, its precise function in the pulmonary microvasculature has remained unclear. In this study, we demonstrate a role for BMP-9 in regulating pulmonary vascular architecture and homeostasis. Our findings reveal that BMP-9 signaling intersects with VEGF pathways and contributes to the delicate balance between vascular growth and remodeling in the lungs. We also show that disruption of this pathway can shift vascular responses toward an HHT-like state, potentially altering disease susceptibility. These insights offer a unique perspective on how BMP-9 and ALK1 shape pulmonary vascular biology and suggest that targeting this axis could inform future strategies for treating complex vascular diseases such as PAH.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Nihel Berrebeh
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Yvon Mbouamboua
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Raphaël Thuillet
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Mina Ottaviani
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Fabien Robert
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Mustapha Kamel Chelgham
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Virginie Magnone
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Agnès Desroches-Castan
Biosanté unit U1292, Grenoble Alpes University, INSERM, CEA
Nicolas Ricard
Biosanté unit U1292, Grenoble Alpes University, INSERM, CEA
Ignacio Anegon
Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Transgenic Rat ImmunoPhenomic facility
Séverine Remy
Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Transgenic Rat ImmunoPhenomic facility
Ralph Theo Schermuly
Department of Internal Medicine, Member of the German Center of Lung Research, Institute for Lung Health (ILH), Justus-Liebig-University of Giessen
Kevin Lebrigand
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Baktybek Kojonazarov
Department of Internal Medicine, Member of the German Center of Lung Research, Institute for Lung Health (ILH), Justus-Liebig-University of Giessen
Laurent Savale
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Marc Humbert
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Sabine Bailly
Biosanté unit U1292, Grenoble Alpes University, INSERM, CEA
Pascal Barbry
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Ly Tu
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)
Christophe Guignabert
INSERM, UMR_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies (HPPIT)