Levels Of 20-Hydroxyeicosatetraenoic Acid In Pulmonary Hypertension Rats And Its Effect On Proliferation Of Pulmonary Arterial Smooth Muscle Cells

Objective:To investigate the levels of 20-Hydroxyeicosatetraenoic acid(20-HETE)in model of pulmonary hypertension(PH)and its effect on the proliferation of pulmonary arterial smooth muscle cells(PASMCs).Methods:Twenty 8-week-old male SD(Sprague-Dawley)rats were divided into a control group and a pulmonary hypertension group.PH was induced by intra-peritoneal injection of20mg/kg monocrotaline(MCT)twice in a week in rats.Mean pulmonary arterial pressure(m PAP)and pulmonary vascular remodeling(WA%,WT%)were assessed at the week 4.The levels of 20-HETE were all analysed by liquid chromatography tandem-mass spectrometry(LC-MS/MS).20-HETE-d6 was used as the internal standardization for 20-HETE.Cultured PASMCs were exposed to different treatments and interventions respectively,including normoxia,hypoxia(3% O2),hypoxia(3% O2)with HET0016 10 u M,normoxia with 20-HETE 100 n M.Ed U test was used to determine the proliferation of PASMCs.Intracellular levels of ROS were detected using DCFH-DA dye.T test or one-way ANOVA were used for data analysis.Results:(1)Increased m PAP,prominent right ventricular hypertrophy,rised WA% and WT% were verified in PH rats;(2)20-HETE levels in serum and lung tissues were significantly lifted in PH rats;(3)20-HETE levels in cell culture supernatants were significantly lifted in hypoxia condition;(4)Proliferation of PASMCs was induced by 20-HETE and hypoxia,and was inhibited by HET0016;(5)Production of ROS was elevated by 20-HETE and hypoxia,and was reduced byHET0016;Conclusion:Vascular remodeling was demonstrated in PH rats and was accompanied with increased20-HETE levels.The pro-proliferative effect induced by 20-HETE may be related to its promotion of ROS expression.