2026-04-13T01:32:09Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1082612025-12-05T09:34:16Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Ola, Roxana author Dubrac, Alexandre author Han, Jinah author Zhang, Feng author Fang, Jennifer S. author Larrivée, Bruno author Lee, Monica author Urarte, Ana A. author Kraehling, Jan R. author Genet, Gael author Hirschi, Karen K. author Sessa, William C. author Viñals Canals, Francesc author Graupera i Garcia-Milà, Mariona author Yan, Minhong author Young, Lawrence H. author Oh, Paul S. author Eichmann, Anne author 2017-03-10T15:14:04Z 2017-03-10T15:14:04Z 2016-11-29 2017-03-10T15:14:04Z Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice. VEGF and PI3K/AKT signalling are increased on Alk1 deletion and BMP9/10 ligand blockade. Genetic deletion of the signal-transducing Vegfr2 receptor prevents excessive angiogenesis but does not fully revert AVM formation. In contrast, pharmacological PI3K inhibition efficiently prevents AVM formation and reverts established AVMs. Thus, Alk1 deletion leads to increased endothelial PI3K pathway activation that may be a novel target for the treatment of vascular lesions in HHT2. Malalties vasculars Rates (Animals de laboratori) Hemorràgia Proteïnes quinases Vascular diseases Rats as laboratory animals Hemorrhage Protein kinases PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia