ELP‐VEGF Treatment Improves the Maternal Syndrome of Preeclampsia in the Dahl Salt Sensitive (S) Rat

Abstract

Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus; however, there is currently no effective treatment for preeclampsia. The anti‐angiogenic protein sFlt‐1 has been implicated in the pathogenesis of preeclampsia through both clinical and experimental studies, leading us and others to propose that antagonism of sFlt‐1 via administration of vascular endothelial growth factor (VEGF) will reduce the maternal symptoms of hypertension and proteinuria in preeclamptic pregnancy. In this study, we tested the hypothesis that VEGF fused to the synthetic carrier elastin like polypeptide (ELP) will improve the maternal syndrome in the Dahl S rat model of superimposed preeclampsia. Female Dahl S rats (16–18 weeks of age) were placed in metabolic cages for 24‐hour urine collection, mated with Dahl S male rats, and randomly divided into control and ELP‐VEGF treated groups. ELP‐VEGF was administered via osmotic pump (5 mg/kg/day, Alzet 2ML1) beginning on day 10 of pregnancy, and pumps were replaced on day 17 of pregnancy. Urine was collected again on day 19, and blood and tissues were harvested on day 20. Urinary protein excretion (Bradford assay) did not differ between groups at baseline (87±11 vs 99±21 mg/d), but was significantly lower during late pregnancy in the ELP‐VEGF treated rats (* p=0.004, table). A subset of ELP‐VEGF‐treated rats (n=4) was implanted with telemetry transmitters (DSI) before mating. While previous studies have shown that blood pressure increases during pregnancy in the Dahl S rat, ELP‐VEGF treatment resulted in a fall in mean arterial pressure of 27±5 mmHg from day 9 to day 18 of pregnancy. No significant differences in fetal growth or litter size were observed following treatment. These data suggest that ELP‐VEGF treatment improves the maternal syndrome of preeclampsia without impairing fetal outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.