Abstract 15404: Eicosapentaenoic Acid Ameliorates Pulmonary Hypertension via G Protein-Coupled Receptor 120 Pathway in Rats
BACKGROUND: Inflammation plays a significant role in pathophysiology of pulmonary hypertension (PH), but the mechanism is not well understood. It is known that omega-3 fatty acids(FA) such as eicosapentaenoic acid (EPA) have beneficial effects on some cardiovascular diseases. Recent report shows that omega-3 FA exerts potent anti-inflammatory effects through G protein-coupled receptor 120 (GPR120). Therefore in our present study, we investigated the effect of EPA in monocrotaline (MCT)-induced PH rats.
METHODS: Forty male Sprague-Dawley rats were given a subcutaneous injection of MCT to induce PH. On day14 and thereafter, the MCT rats were given daily oral administration of EPA(5g/kg/day, EPA group) or vehicle(MCT group). 20 other rats were administered EPA only.
RESULTS: In in vivo study, the survival rate at day 30 in the EPA group markedly improved compared with that of the MCT group (42% vs 3%, p<0.01). The EPA group rats showed lower systolic pulmonary arterial pressure than the MCT group in cardiac catheterization (45.4±11.5mmHg vs 89.5±6.2mmHg, p<0.01). Furthermore medial hypertrophy of small pulmonary arteries (PA) remarkably improved in the EPA group in immunohistochemsitry. In mRNA expressions, the levels both transforming growth factor-beta (TGF-beta) and fibroblast growth factor 2 (FGF2) were reduced in the EPA group compared with those levels of the MCT group. In in vitro study, EPA inhibited dose-dependently pulmonary arterial smooth muscle cells (PASMCs) proliferation stimulated with TGF-beta or FGF2. EPA also suppressed nuclear factor-kappa B p65 translocation into the nucleus in PASMCs. Interestingly, immunohistochemistry revealed that the expression of GPR120 in PA was much stronger in the EPA group than in the MCT group. GPR120 mRNA expressions in lung tissue were increased in EPA group compared with MCT group. GW9508 (GPR120 agonist) suppressed PASMC proliferation stimulated with FGF2 while the antagonist partially canceled this effect, suggesting that anti-inflammatory effect of EPA through GPR120 contribute to the improvement of PH.
CONCLUSION: We elucidated that EPA had anti-inflammatory effects through GPR120 in PH rat models. EPA has potential as a new therapeutic tool for PH.
- © 2013 by American Heart Association, Inc.