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• W2530124743 abstract "Introduction: Adventitial fibroblast proliferation, mediated by p38 mitogen-activated protein kinase (p38 MAPK), contributes to vascular remodelling in pulmonary arterial hypertension (PAH). Bone Morphogenetic Protein type-2 Receptor (BMPR2) mutations cause PAH. MicroRNA-155 over expression down regulates Smad5, a key intermediary in the BMPR pathway. Hypothesis: MicroRNA-155 down regulation influences signalling pathways relevant in the development of PAH, ameliorating the pathological phenotype in vitro and in vivo. Methods: Pulmonary adventitial fibroblasts (PAFs) were isolated from miR-155 knockout (miR-155 -/- ) and wild type (WT) mice. The effect of acute hypoxia on signalling pathways was assessed using Western blotting. PAF proliferation was evaluated by [ 3 H] thymidine incorporation. WT and miR-155 -/- mice were subjected to chronic hypoxia, or maintained in normal conditions. Right ventricular systolic pressure (RVSP) and RVH were measured to assess the development of pulmonary hypertension. Results: Increased Smad5 signalling was seen in miR-155 -/- PAFs in normal and hypoxic conditions, compared with WT controls. Hypoxia led to enhanced p38 MAPK activity in WT PAFs, but not in miR-155 -/- PAFs. WT mice developed elevated RVSP in hypoxia as expected. MiR-155 -/- mice exposed to the same degree of hypoxia had significantly lower RVSP than WT controls (31.9mmHg vs 38.6mmHg; P=0.0105). A trend towards less hypoxia-induced RVH was seen in miR-155 -/- mice, versus WT mice. Conclusion: Signalling pathways important in pulmonary vascular remodelling are influenced by miR-155. In vivo, this appears to partially protect against the development of pulmonary hypertension." @default.
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• W2530124743 date "2015-09-01" @default.
• W2530124743 modified "2023-09-23" @default.
• W2530124743 title "Elucidating signalling pathways in pulmonary hypertension using a microRNA knockout mouse model – In vitro and in vivo data" @default.
• W2530124743 doi "https://doi.org/10.1183/13993003.congress-2015.pa592" @default.
• W2530124743 hasPublicationYear "2015" @default.
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