Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;122(26):e2410229122.
doi: 10.1073/pnas.2410229122. Epub 2025 Jun 23.

Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling

Nihel Berrebeh  1   2 , Yvon Mbouamboua  3 , Raphaël Thuillet  1   2 , Mina Ottaviani  1   2 , Fabien Robert  1   2 , Mustapha Kamel Chelgham  1   2 , Virginie Magnone  3 , Agnès Desroches-Castan  4 , Nicolas Ricard  4 , Ignacio Anegon  5 , Séverine Remy  5 , Ralph Theo Schermuly  6 , Kevin Lebrigand  3 , Baktybek Kojonazarov  6 , Laurent Savale  1   2   7 , Marc Humbert  1   2   7 , Sabine Bailly  4 , Pascal Barbry  3   8 , Ly Tu #  1   2 , Christophe Guignabert #  1   2
Affiliations

Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling

Nihel Berrebeh et al. Proc Natl Acad Sci U S A. 2025 Jul.

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.

Keywords: ALK1; VEGF; pulmonary hypertension; pulmonary microvasculature; pulmonary vascular remodeling.

PubMed Disclaimer

Conflict of interest statement

Competing interests statement:Over the last three years, C.G. reports grants from Acceleron Pharma (Cambridge, MA), a wholly-owned subsidiary of Merck & Co., Inc. (Rahway, NJ), MSD, Corteria, Structure therapeutics (ex ShouTi), and Diagonal Therapeutics, outside the submitted work. M.H. reports grants and personal fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX and United Therapeutics, outside the submitted work. Over the last three years, C.G. reports grants from Acceleron Pharma (Cambridge, MA), a wholly-owned subsidiary of Merck & Co., Inc. (Rahway, NJ), MSD, Corteria, Structure therapeutics (ex ShouTi), and Diagonal Therapeutics, outside the submitted work. M.H. reports grants and personal fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX and United Therapeutics, outside the submitted work.

Similar articles

See all similar articles

Cited by

References

    1. Guignabert C., et al. , Pathology and pathobiology of pulmonary hypertension: Current insights and future directions. Eur. Respir. J. 64, 2401095 (2024), 10.1183/13993003.01095-2024. - DOI - PMC - PubMed
    1. Humbert M., et al. , ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 61, 2200879 (2023). - PubMed
    1. Boucly A., et al. , Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur. Respir. J. 50, 1700889 (2017). - PubMed
    1. Shovlin C. L., et al. , The European rare disease network for HHT: Frameworks for management of hereditary haemorrhagic telangiectasia in general and specialty care. Eur. J. Med. Genet. 65, 104370 (2022). - PubMed
    1. Robert F., Desroches-Castan A., Bailly S., Dupuis-Girod S., Feige J. J., Future treatments for hereditary hemorrhagic telangiectasia. Orphanet. J. Rare Dis. 15, 4 (2020). - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources