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Rats with hypertension, hemolysis, elevated liver enzymes and low platelets (HELLP) have increased placental and circulating FASL (LB713)
The Faseb JournalPeer ReviewedWallace Kedra +42014Journals
The CD95L or FASL system of apoptosis is part of the tumor necrosis factor family that contributes to cell death. Placental CD95L is up‐regulated in women with HELLP syndrome and has been proposed to contribute to the liver damage seen in these patients. The objective of the current study was to determine if animals with HELLP have increased CD95L similar to women with HELLP. Additionally, as the anti‐inflammatory drug dexamethasone has been found to decrease inflammation in women with HELLP we also examined its’ effects on circulating CD95L in women with HELLP. Whole blood was collected from women with HELLP before and 24hrs after dexamethasone administration (10mg per 12hr intravenously). On gestational day (GD) 12, sEndoglin (7ug/kg/day) and sFlt‐1 (4.7ug/kg/day) infusion began via mini‐osmotic pump into normal pregnant (NP) rats. On GD18 carotid catheters were inserted, GD19 plasma and tissue were collected and CD95L was measured via western blot or enzyme linked immunosorbent assay. Women with HELLP had significantly higher levels of circulating CD95L compared to NP women (132.7 + 35 vs. 29.11 + 16; n=6;P=0.02). HELLP rats had significantly more circulating CD95L compared to NP rats (179.6 + 24 vs. 117.1 + 13pg; n=5; P=0.05). HELLP rats also had increased production of placental CD95L as measured via western blot (17.97 + 3 vs. 9.45 + 2.7 O.D.). These data suggest that similar to women with HELLP syndrome, rats with HELLP syndrome have increased circulating CD95L. Future studies will examine the effects of dexamethasone on decreasing CD95L production.
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