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Bone Morphogenetic Protein-9 Controls Pulmonary Vascular Growth and Remodeling

Title: Bone Morphogenetic Protein-9 Controls Pulmonary Vascular Growth and Remodeling
Authors: Berrebeh, Nihel; Mbouamboua, Yvon; Thuillet, Raphaël; Ottaviani, Mina; Robert, Fabien; Kamel Chelgham, Mustapha; Magnone, Virginie; Desroches-Castan, Agnès; Ricard, Nicolas; Anegon, Ignacio; Remy, Séverine; Schermuly, Ralph Theo; Lebrigand, Kevin; Kojonazarov, Baktybek; Savale, Laurent; Humbert, Marc; Bailly, Sabine; Barbry, Pascal; Tu, Ly; Guignabert, Christophe
Contributors: Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Institut de pharmacologie moléculaire et cellulaire (IPMC); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA); BioSanté (UMR BioSanté); Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA); Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Department of Internal Medicine, Member of the German Center of Lung Research (DZL), Justus-Liebig-University of Giessen (JLU), Giessen, Germany; Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Source: ISSN: 0027-8424.
Publisher Information: CCSD; National Academy of Sciences
Publication Year: 2025
Subject Terms: Pulmonary Vascular Remodeling; Pulmonary Microvasculature; Pulmonary Hypertension; VEGF; ALK1; [SDV]Life Sciences [q-bio]
Description: International audience ; 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40549904; PUBMED: 40549904; PUBMEDCENTRAL: PMC12232436
DOI: 10.1073/pnas.2410229122
Availability: https://hal.science/hal-05190343; https://hal.science/hal-05190343v1/document; https://hal.science/hal-05190343v1/file/BMP-9%20controls%20pulmonary%20vascular%20growth%20and%20remodeling.pdf; https://doi.org/10.1073/pnas.2410229122
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.5CD44993
Database: BASE