TY - JOUR T1 - The inflammasome adaptor ASC mediates pulmonary artery remodelling JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2015.PA4908 VL - 46 IS - suppl 59 SP - PA4908 AU - Fadila Telarevic Cero AU - Karl Otto Larsen AU - Vigdis Hillestad AU - Maria Belland Olsen AU - Camilla Udjus AU - Ivar Sjaastad AU - Arne Yndestad AU - Pål Aukrust AU - Else Marit Løberg AU - Geir Christensen AU - Ole Henning Skjønsberg Y1 - 2015/09/01 UR - http://erj.ersjournals.com/content/46/suppl_59/PA4908.abstract N2 - Background: Inflammasomes are large multiprotein oligomers consisting of a receptor (such as NLRP3), the adaptor protein (ASC) and caspase-1. Assembly of the inflammasome activates caspase-1 which cleaves interleukin (IL)-18 and IL-1β to their bioactive forms. Elevated levels of IL-18 and IL-1β are found in patients with pulmonary hypertension, and increased levels of IL-18 have been found in alveolar hypoxia which leads to pulmonary hypertension.Objective: To study the role of ASC in chronic hypoxia-induced pulmonary artery remodelling.Methods: WT, NLRP3-/- and ASC-/- mice were exposed to 3 months of hypoxia in a tightly sealed chamber containing 10% oxygen. Right ventricular systolic pressure (RVSP) was measured with a microtipped transducer catheter. To quantify muscularization and collagen content of arteries, lung sections were stained with von Willebrand factor, smooth muscle α-actin, acid fuchsin orange G-stain (AFOG) and Sirius Red.Results: ASC-/- mice exposed to hypoxia had significantly lower RVSP than WT hypoxic mice, indicating reduced pulmonary hypertension. RVSP of NLRP3-/- exposed to hypoxia was not altered compared to WT hypoxia. Hypoxic ASC-/- mice showed less degree of muscularization and fibrosis around pulmonary arteries compared to WT mice exposed to hypoxia.Conclusions: Depletion of the inflammasome adaptor ASC diminish pulmonary artery remodelling in hypoxia-induced pulmonary hypertension. ER -