TY - JOUR T1 - Loss of Bmp9 does not lead to spontaneous pulmonary hypertension, but attenuates vascular remodeling in experimental models JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.3558 VL - 56 IS - suppl 64 SP - 3558 AU - Nihel Berrebeh AU - Raphaël Thuillet AU - Ly Tu AU - Benjamin Le Vely AU - Amélie Cumont AU - Ignacio Anegon AU - Alice Huertas AU - Marc Humbert AU - Sabine Bailly AU - Christophe Guignabert Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/3558.abstract N2 - Introduction: Despite increasing evidence suggesting that the Bone Morphogenetic Protein (BMP)-9 signaling pathway is playing a role in the pulmonary hypertension (PH) pathogenesis, the data in the literature are still controversial.Aims and Objectives: To investigate the role of BMP9 signaling pathway in PH pathophysiology.Methods: Bmp9 KO-/- rats were subjected to 3 distinct well characterized experimental PH models: the chronic hypoxia (CHx), monocrotaline (MCT) and Sugen/hypoxia (SuHx) models. Wild-type littermates were used as controls. We then performed transthoracic echocardiography and right heart catheterization as well as histological analyses in these 3 models: 21 days after CHx and MCT treatment and 8 weeks in the SuHx model.Results: While Bmp9 KO-/- rats did not develop any spontaneous phenotype, they were protected against PH induced in our 3 different PH models, compared with their wild-type littermates, as reflected by lower values of mean pulmonary artery pressure (mPAP), total pulmonary vascular resistance (TPVR), and Fulton index. We also found a less pronounced remodeling of the pulmonary arterioles and collagen accumulation in the right ventricle in these Bmp9 KO-/- rats compared to their wild-type littermates. Finally, we found that the in vitro exposure of human pulmonary endothelial cells (ECs) to BMP9 modulates the secretion of pro- and anti-angiogenic factors. These in vitro observations were confirmed in vivo, with Bmp9 KO-/- rats exhibiting increased serum and lung levels of pro-angiogenic factors.Conclusions: BMP9 deficiency does not lead to spontaneous PH, but attenuates the development of experimental PH.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3558.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -