Abstract 17778: Estrogen-induced Rescue of Pre-existing Severe Pulmonary Hypertension is Associated with Restoration of Elevated Plasma Oxidized Lipids and Eicosanoids
Introduction: Pulmonary hypertension (PH) is a chronic debilitating lung disease associated with pulmonary vascular dysfunction. Oxidized-lipoproteins and eicosanoids have been shown to play a key role in the pathogenesis of vascular disease in atherosclerosis, yet their role in PH is not fully known. Recently we have reported that 17-beta estradiol or estrogen (E2) rescues pre-existing severe PH. Here we investigated whether PH is associated with increased plasma levels of oxidized-lipids and eicosanoids, and if E2 can restore their levels.
Methods: Rats received a single injection of monocrotaline (MCT, 60 mg/kg, s.c.) or PBS (CTRL, n=8) at day 0. Severe PH was established 21 days after MCT (PH group, n=8). At this time point rats were either euthanized or received E2 therapy for 10 days until day 30 (42.5 ug/kg/day, s.c., n=8). Cardiac catheterization was performed terminally to record RV pressure (RVP). Biological oxidation products of arachidonic acid, linoleic acid and eicosanoides including hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), prostaglandins (PGs) and thromboxanes (TXs) were determined in the plasma by mass spectrometry. Values are expressed as Mean±SE.
Results: MCT injected rats developed severe PH by day 21 (RVP=68±2 vs. 31±2 mmHg in CTRL, p<0.01) and as expected E2 therapy rescued PH (RVP=38±1 mmHg, p<0.01 vs. PH). PH was associated with increased plasma levels (pg/ml of plasma) of 9-HODE (2217±381 vs. 1205±224 in CTRL, p<0.05) and 13-HODE (4347±439 vs. 2017±504 in CTRL, p<0.05). E2 reversed PH-induced increase in HODEs (9-HODE=976±259; 13-HODE=2469±531; p<0.05 vs. PH for all). PH led to significantly elevated plasma 5-HETE (938±77 vs. 672±14), 12-HETE (9720±972 vs. 7326±473) and 15-HETE (818±62 vs. 549±11; p<0.05 vs. CTRL for all). E2 fully reversed the increase in HETEs (5-HETE=708±37; 12-HETE=6981±248; 15-HETE=622±50; p<0.05 vs. PH for all). PH also led to elevated plasma TXB2 (3.5±0.2 vs. 2.2±0.1), PGD2 (98±11 vs. 34±6) and PGE2 (27±1 vs. 13±2; all p<0.05 vs. CTRL) and E2 restored their levels (TXB2=2.6±0.2; PGD2=54±10; PGE2=19±2; all p<0.05).
Conclusions: Severe PH is associated with increased levels of plasma oxidized lipids and eicosanoids that are fully restored by E2 therapy.
- © 2012 by American Heart Association, Inc.