Abstract
Preeclampsia (PE) is associated with new onset of hypertension and proteinuria and affects 2–8% of pregnancies worldwide. It is a leading cause of maternal and fetal morbidity and mortality with no current therapy to manage the disease. While its etiology is yet to be elucidated, immune system activation of various inflammatory pathways is reported to be a contributing factor. Toll‐like receptor (TLR) activation by damage‐associated molecular patterns (DAMPS) released following poor placentation and oxidative stress has been linked to the development of PE and TLR4 expression is increased in the placenta of preeclamptic women. We performed a whole transcriptomic analysis on placental tissues from gestation day (GD) 14 rats using Affymetrix Rat 2.0ST GeneChip and noted significant dysregulation in multiple genes during pregnancy in the Dahl salt sensitive (S) rat, a model of spontaneous superimposed preeclampsia, compared to the normal pregnant control Sprague Dawley (SD) rat. These genes included upregulation of TLR4 in the placenta of Dahl S rats (1.9 fold, p<0.05), which was subsequently confirmed via quantitative real‐time PCR (2.9 fold, p<0.05). To further investigate this pathway, the goal of this study was to assess the effect of TLR4 inhibition in pregnant Dahl S rats. Curcumin, the anti‐oxidant and anti‐inflammatory active ingredient in the spice turmeric, has been reported to inhibit TLR4 activation, and reduced blood pressure in rodent models of LPS‐induced preeclampsia. We hypothesized that curcumin would inhibit TLR4 activation and reduce blood pressure and uterine artery resistance index during pregnancy in the Dahl S rat. Starting on gestational day (GD) 10, 17 weeks old rats were divided into two groups: a treated group (N=7) that orally received dough containing 400mg/kg of curcumin daily and a control group (N=6) that received the vehicle dough through GD20. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler ultrasound. On GD20, terminal blood pressure measurements were taken, and pups and placentas harvested and measured. Curcumin had no effect on UARI (0.78 vs. 0.82, p=0.4) or mean arterial pressure (146 ± 5 vs. 133 ± 5 mmHg, p=0.08). Fetal outcome assessed by litter size (10 ± 1 vs. 11 ± 1 pups); pup weight (2.23 ± 0.08 vs. 2.30 ± 0.07 g) and pup length (29.44 ± 0.31 vs. 29.6 ± 0.46 cm) was similar between groups. These results suggest that administration of curcumin does not alleviate the preeclamptic phenotype in the Dahl S rat.Support or Funding InformationR01HL1347111R01HL137673This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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