TY - JOUR T1 - Lung heparan and chondroitine sulfate imbalance, and functional changes in pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P304 AU - Benoit Ranchoux AU - Emilie Henault AU - Sébastien J. Dumas AU - Sandrine Chantepie AU - David Montani AU - Barbara Girerd AU - Alix Blanchet de la Sablière AU - Elie Fadel AU - Philippe Dartevelle AU - Dulce Papy-Garcia AU - Marc Humbert AU - Frederic Perros AU - Patricia Albanese AU - Sylvia Cohen-Kaminsky Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P304.abstract N2 - BackgroundIn pulmonary arterial hypertension (PAH) endothelial cell dysfunction, smooth muscle cell (SMC) proliferation and altered extracellular matrix (ECM) participate to lung arterial remodeling. Sulfated glycosaminoglycans (GAGs) such as heparan sulfate (HS) and chondroitin sulfate (CS) are essential components of the ECM in lung development.Working hypothesisHS and CS control cell migration and proliferation through selective binding of chemokines and growth factors. We hypothesized that changes in GAG pattern in PAH lung could participate to vascular remodeling.MethodsWe performed quantitative (HS/CS ratio, total amount), and functional analysis (growth factor binding, cell proliferation) of HS and CS extracted from lungs of PAH patients and controls, and of monocrotaline PH ratsResultsLungs of HTAPi, HTAPh and MVO patients, revealed specific patterns of HS/CS accumulation and imbalance. GAG interaction with growth factors, modulation of SMC proliferation and expression of GAG biosynthetic enzymes are in progress. PH rats showed a 2.5 fold increase of GAGs/mg lung, preceding vascular remodeling and due to HS increase at day1 followed by CS at day7. These changes were correlated to significant functional modifications of GAG binding to growth factors (VEGF, FGF-2).ConclusionsChanges of GAG composition in PAH lung could lead to deregulated vascular cell proliferation and maintain a chronic inflammatory and vascular remodeling process. ER -