Abstract 279: Hypertension in Hemolysis, Elevated Liver Enzyme, Low Platelet Syndrome is Associated with Increased Endothelin-1

Abstract

INTRODUCTION. HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe form of preeclampsia, a hypertensive disorder that occurs during pregnancy. We have shown that HELLP syndrome in both women and in an animal model causes hypertension and elevated TNF-α, IL-6, and agonistic autoantibodies to the angiotensin II receptor, all of which have been shown to activate the endothelin-1 system (ET-1). Therefore we tested the hypothesis that hypertension in response to HELLP syndrome is associated with ET-1 activation. METHODS. Plasma was collected from women with HELLP syndrome or pregnant women without maternal/fetal complications at the time of delivery. Endothelin (ET-1) was extracted from the plasma and measured with a Quantikine ET-1 enzyme linked immunosorbent assay kit. On gestational day (GD) 12 miniosmotic pumps infusing sEndoglin (7ug/kg/day) and sFlt-1 (4.7ug/kg/day) were implanted into normal pregnant rats to induce HELLP syndrome. On GD18 carotid catheters were inserted into HELLP and normal pregnant (NP) rats and mean arterial pressure (MAP) was recorded on GD19; serum, urine and tissues were collected for molecular analysis. RESULTS. Women with HELLP syndrome (n=4) had significantly more circulating ET-1 (3.35pg/mL) compared to normal pregnant women (0.75pg/mL; n=3; p=0.006) and increased MAP (120.8±6.2 mmHg HELLP vs. 87.33±6.67mmHg NP; p=0.015). In rats MAP increased from 91±2mmHg in NP rats (n=4) to 129.8±4.5mmHg in HELLP rats (n=4; p=0.0002). Preproendothelin mRNA expression was 3 fold higher in placentas and 1.3 fold higher in livers from HELLP rats compared to NP rats (p=0.02; p=0.05). In addition we measured ET-1 secretion from endothelial cells exposed to serum from NP and HELLP rats. ET-1 in response to NP serum was 4.03±.68pg/mg/mL and increased to 9.69±3.5pg/mg/mL with HELLP serum (p=0.04) after 24hrs. CONCLUSION. These data support the hypothesis that hypertension in both women and animals with HELLP syndrome is accompanied by increased ET-1 expression.