BMP9 & BMP10: two key players in vascular quiescence and rare vascular diseases (in english)

Vascular vessels play key roles in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. In adult, endothelial cells are quiescent. This vascular quiescence is regulated by organ-specific signaling pathways which can lead to many pathologies when dysfunctional (diabetes, age-related macular degeneration, ischemia, …). Our team works on of these signal pathways, the BMP (Bone morphogenetic proteins) signalling pathway whose mutations lead to a rare vascular disease called Hemorrhagic Hereditary Telangiectasia (HHT). This disease is due to loss-of-function of two transmembranous receptors ALK1 (activin receptor-like kinase 1) and endoglin. In 2007, our team identified the two high affinity ligands (BMP9 and BMP10) of this orphan signaling complex.  Since then, we have studied their roles using in vitro and in vivo models. We could show that this pathway plays a key role in vascular quiescence and could propose that this disease is due to an activation of vascular remodeling. In 2012, we performed the first clinical trial repurposing an anti-angiogenic drug (bevacizumab, an anti-VEGF antibody) that significantly ameliorated the symptoms of HHT patients which is still the best option for these patients. We have also developed functional tests for these mutant proteins that are now used in several hospitals and that allowed a better understanding of these proteins.