Hypertension in a rat model of HELLP Syndrome is associated with Increased TNF‐alpha, IL‐6 and CD4+ T cell activation

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a hypertensive disorder that can occur during pregnancy with severe symptoms and consequences, however, the physiological mechanisms involved are unknown. Our previous studies have shown that women with HELLP syndrome have elevated sFlt‐1, sEndoglin, TNF‐α and IL‐6. In this study we utilized a HELLP syndrome rodent model to determine if immune activation occurs similarly to that seen in HELLP patients.On gestational day (GD) 12, sEndoglin (7ug/kg/day) and sFlt‐1 (4.7ug/kg/day) infusion began via miniosmotic pump into normal pregnant (NP) rats. On GD18 carotid catheters were inserted, GD19 mean arterial pressure (MAP), plasma and tissue collected.MAP increased from NP (n=21) 101.1±1.7 to 113.4±3.2mmHg in HELLP rats (n=14; P<.05). Liver enzymes increased from 46.3±6.9 in NP to 63.8±4.6 IU/L in HELLP rats (P<.05) and platelets decreased in HELLP rats (7112±657.9uL) vs. NP rats (28714+5236uL, P<.5). TNFα and IL‐6 were increased in HELLP rats (54.7±12.6 vs. 25.6±3.5pg/mL; P<.5) and (103.6±26.5 vs. 40.2±8.2pg/mL; P<.05) compared to NP rats. HELLP rats had increased CD4+ T lymphocytes compared to NP rats, circulating 20.7 to 8.9% (P<.5); spleen 7.1 to 4.9% and liver 14.7 to 3.8% gated.In this study we demonstrate that hypertension in a rat model of HELLP syndrome, is associated with a T helper 1 immune activation similar to that seen in HELLP patients.