TY - JOUR T1 - Siah2 in pulmonary hypertension and right ventricular hypertrophy JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P494 AU - Daniela Haag AU - Dorothea M. Peters AU - Bakytbek Kojonazarov AU - Simone Kraut AU - Hossein A. Ghofrani AU - Ralph T. Schermuly AU - Werner Seeger AU - Friedrich Grimminger AU - Andreas Möller AU - M. Lienhard Schmitz AU - Norbert Weissmann Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P494.abstract N2 - Pulmonary hypertension (PH) is a disease of multifactorial etiology, which has a poor prognosis. It results in right heart hypertrophy which can culminate in decompensation and death. This study investigated the role of seven in absentia homologue 2 (Siah2) ubiquitin ligase in the pathogenesis of pulmonary vascular and right ventricular (RV) remodelling. Siah2 regulates Hypoxia-inducible factor-1α (HIF-1α) which plays a pivotal role in the pathogenesis of PH and RV hypertrophy by influencing cell metabolism, proliferation, survival and tissue vascularisation. Siah2 knockout (ko) mice and wildtype (wt) controls were examined in a model of hypoxia-induced PH and in pulmonary artery banding (PAB) which induces RV pressure overload independently of pulmonary vascular changes. Hypoxia-treated mice were kept in 10% O2 for 4 weeks. PAB-operated mice received a clip on the pulmonary artery and were examined after 3 weeks. Hypoxic Siah2 ko mice showed reduced RV hypertrophy and improved RV function (determined by echocardiography) compared to wt mice; however, both showed similarly increased pulmonary vascular remodelling. Siah2 ko PAB mice showed less RV hypertrophy and a partially conserved RV function. Fibrosis in the RV, determined by quantification of collagen, was significantly reduced in PAB Siah2 ko mice compared to wt mice. However, Siah2 mRNA expression was not altered in hypoxic lungs and RVs as well as in PAB-RVs of wt mice. Protein- and mRNA-expression of vegfa, a target gene of HIF1α important for neoangiogenesis, did not show any regulation in both models. In conclusion, even though Siah2 crucially influences cardiac function, it does not seem to play a role in the pulmonary pathology of PH. ER -