TY - JOUR T1 - Therapeutic potential of DMHCA for pulmonary arterial hypertension (PAH) JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P492 AU - Laima Taraseviciene-Stewart AU - Maike Leberl AU - Zakaria Moumen AU - Rajendra Kadam AU - Uday Kompella AU - Martin Zamora AU - Adelheid Kratzer Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P492.abstract N2 - Introduction: Severe PAH is a fatal, multifactorial vascular disease that is characterized by lung vascular remodeling, disordered angiogenesis, high pulmonary artery blood pressure (PAP) and right ventricular hypertrophy. Currently there are no effective therapies and new therapeutical strategies are urgently needed.Objective: Recently we found that in PAH there is impairment in Liver X receptor (LXR) function. LXR is a known regulator of lipid metabolism, angiogenesis and inflammation. Here we investigate whether treatment with synthetic steroidal LXR activator N,N-dimethyl-3b-hydroxy-cholenamide (DMHCA) encapsulated into microparticles (DMHCA-MP) can attenuate inflammation, disordered angiogenesis and the development PAH.Methods: Sprague Dawley rats were exposed to hypobaric hypoxia (18000 ft = 5,000 m altitude) for 3 weeks. Rats were divided into 4 groups: 1) untreated (Hx); 2) VEGF receptor inhibitor SUGEN5416 (20mg/kg) treated; 3) pre-treated with DMHCA-MP one week prior to exposure to SUGEN5416; 4) DMHCA-MP. PAP, hematocrit, right ventricle hypertrophy, inflammation and LXR, VEGF, VEGFR2 expression levels were determined.Results: Exposure to hypoxia and SU5416/hypoxia significantly increased hematocrit values and RV/(LV+S) ratios when compared to normoxic control group and downregulated VEGF and VEGFR2 expression. Pretreatment with DMHCA-MP blocked the development of PAH, normalized the hematocrit, and significantly decreased inflammation.Conclusions: Our findings suggest that LXR is a potential therapeutic target for PAH. LXR activation might have a fundamental protective effect against the development of PAH.Funded by AHA 0735388N, 11GRNT7520020, FAMRI CIA 072053 and Emphysema Research Fund. ER -