PT - JOURNAL ARTICLE AU - Matthias Brock AU - Michelle Trenkmann AU - Colin Schwarzwald AU - Silvia Ulrich AU - Max Gassmann AU - Louise Ostergaard AU - Steffen Gay AU - Rudolf Speich AU - Lars Huber TI - AntagomiR directed against miR-20a restores BMP signaling in hypoxia-induced pulmonary hypertension in vivo DP - 2011 Sep 01 TA - European Respiratory Journal PG - p4756 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p4756.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p4756.full SO - Eur Respir J2011 Sep 01; 38 AB - Introduction: Dysregulated expression of the bone morphogenetic protein (BMP) receptor type II (BMPR2) is a pathogenetic hallmark in the development of pulmonary hypertension (PH). We recently demonstrated that microRNA 20a (miR-20a) represses the expression of BMPR2. Here we investigated the therapeutic potential of antagonizing miR-20a in an in vivo model of PH.Methods: For in vivo inhibition of miR-20a, antagomiR-20a (A-20a) was injected intraperitoneally into mice with hypoxia-induced PH. After three weeks of hypoxia, morphometry and blood gas analysis were performed. RNA levels of miR-20a, BMPR2, Smad5, and Id2 were assessed by real-time PCR in hearts and lungs.Results: Intraperitoneal injection of A-20a resulted in significant down regulation of miR-20a in lungs. When exposed to hypoxia, animals treated with A-20a developed less right ventricular hypertrophy as evidenced by relative heart weight. Treatment with A-20a reduced the hemoglobin levels and, moreover, the acid-base status (base deficit) approached the baseline values of normoxic animals. Molecular analysis showed down regulation of BMPR2 mRNA levels in lung tissue by hypoxia (0.79±0.24 fold, p=0.039). A-20a abrogated the hypoxia induced down regulation of BMPR2 and led to significant up regulation of BMPR2 (1.62±0.18 fold, p<0.001). We detected increased expression of Smad5 (1.29±0.19 fold, p=0.003) and the BMP target gene Id2 (1.43±0.40 fold, p=0.02) in lung tissue of A-20a treated mice suggesting improved BMP signaling.Conclusion: Our data underpin the importance of miR-20a in the BMP signaling and emphasize the need for further studies to address the therapeutic potential of antagomiRs for the human disease.