Abstract 176: Hypertension in a Rat Model of HELLP Syndrome is Associated with T Helper 1 Type Immune Activation

Abstract

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a severe form of preeclampsia, which is a hypertensive disorder that occurs during pregnancy. While the symptoms and consequences of HELLP syndrome are often severe, the physiological mechanisms involved are still unknown. Previous studies demonstrate that simultaneously elevated sFlt-1 and sEndoglin, causes symptoms similar to HELLP syndrome in pregnant rats. In this study we utilized this HELLP syndrome rodent model to determine if an immunological cascade occurs similarly to that seen in HELLP patients. On gestational day (GD) 14 miniosmotic pumps infusing sEndoglin (7ug/kg/day) and sFlt-1 (3.7ug/kg/day) were implanted into normal pregnant (NP) rats. On GD18 carotid catheters were inserted and mean arterial pressure (MAP) was recorded on GD19. Plasma and tissue was also collected to determine adverse pathology and markers of inflammation. MAP increased from NP (n=7) 104+3 to 122+3mmHg in HELLP rats (n=14) (P=0.002). Alanine aminotransferase liver enzymes were also increased from 37.78+4.5 IU/L in NP to 62.85+6.1 IU/L in HELLP rats (P=0.007) and platelets were decreased in HELLP rats (6286+1209uL) compared to NP rats (28375+4547uL, P = 0.0007). TNF alpha and IL-6 were increased in HELLP rats (54.74+12.67pg/mL vs. 25.65+3.5pg/mL n=8; P = 0.04) and (103.6+26.5pg/mL vs. 40.18+ 8.2pg/mL/ P = 0.04) compared to NP rats. Furthermore, HELLP rats had increased CD4+ T lymphocytes compared to NP rats, circulating 14.37% vs. 9% gated; placental 8.67% vs. 5.99% gated; spleen 12.4% vs. 7.84% gated; liver 8.27% vs. 1.7% gated. In this study we demonstrate that hypertension in a newly adapted rat model of HELLP syndrome, is associated with a T helper 1 immune activation similar to that seen in HELLP patients.