Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling

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.

• Berrebeh, N.
• Mbouamboua, Y.
• Thuillet, R.
• Ottaviani, M.
• Robert, F.
• Kamel Chelgham, M.
• Magnone, V.
• Desroches-Castan, A.
• Ricard, N.
• Anegon, I.
• Remy, S.
• Schermuly, R. T.
• Lebrigand, K.
• Kojonazarov, B.
• Savale, L.
• Humbert, M.
• Bailly, S.
• Barbry, P.
• Tu, L.
• Guignabert, C.