Abstract P092: Proliferation of Endogenous T-regulatory Cells Improves the Pathophysiology Associated with Placental Ischemia of Pregnancy
Preeclampsia (PE), new onset hypertension during pregnancy, is associated with pro-inflammatory cytokines and decreased regulatory immune mechanisms such as Tregs, IL-10 and IL-4. We believe this decrease in immune regulatory mechanisms leads to an uncontrolled proinflammatory response which contributes to most of the pathophysiology associated with PE. The Reduced Uterine Perfusion Pressure, RUPP, rat model of induced placental ischemia exhibits similar characteristics as women with PE including high blood pressure, elevated pro-inflammatory cytokines and cells and decreased Tregs, IL-4 and IL-10. Therefore, we hypothesized that stimulating Tregs by administration of a superagonist (SA) would increase the Treg profile in the RUPP rats which could reduce pro-inflammatory cytokines and blood pressure. The RUPP procedure was performed at gestation day 14 (GD14); SA was administered intraperitoneally at GD15, GD18 carotid catheters inserted, and GD19 MAP and pup weight, serum and tissues were collected. MAP in NP rats was 91 +/- 3, 119.6 +/- 2 in RUPPs which was improved to 111 +/- 1 mmHg in RUPP+SA. Circulating FoxP3+ Treg cells were 6 +/- 1.7% in NP, 0.77% +/- 0.75 in RUPP rats but increased to 11% +/- 3 in RUPP+SA; IL-6 was 33.65+/- 3.4 in NP, 117.2 +/- 37.8 in RUPP, and 43.66+/- 6.1 pg/mL in RUPP+SA. Placental Pre-pro Endothelin-1 (PPET-1) was increased 44.42+/- 0.269 fold in RUPP compared to NP 1+/- 0.255, but was decreased to 18.78+/- 0.48 in RUPP+SA. These data suggest an important role for up-regulating Treg cells to enhance the immune regulatory interactions and lower the hypertension without causing further reduction in fetal weight in response to placental ischemia during pregnancy.
Author Disclosures: T. Ibrahim: None. L. Przybyl: None. A.C. Harmon: None. D.C. Cornelius: None. M.W. Cunningham: None. L.M. Amaral: None. J.L. Faulkner: None. R. Dechend: None. B. LaMarca: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; NIH.
- © 2015 by American Heart Association, Inc.