Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling

• 成果类型: Article
• 署名作者: Berrebeh, Nihel; Mbouamboua, Yvon; Thuillet, Raphael; Ottaviani, Mina; Robert, Fabien; Chelgham, Mustapha Kamel; Magnone, Virginie; Desroches-Castan, Agnes; Ricard, Nicolas; Anegon, Ignacio; Remy, Severine; Schermuly, Ralph Theo; Lebrigand, Kevin; Kojonazarov, Baktybek; Savale, Laurent; Humbert, Marc; Bailly, Sabine; Barbry, Pascal; Tu, Ly; Guignabert, Christophe
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CEA; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Nantes Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Justus Liebig University Giessen; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Antoine-Beclere - APHP; Universite Paris Saclay; Hopital Universitaire Bicetre - APHP; Universite Cote d'Azur
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14518
• DOI: 10.1073/pnas.2410229122
• 发表日期: 2025-07-01
• 关键词: ldl transcytosis; kinase 1; angiogenesis; expression; bmp9; hypertension; alk1

摘要

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.