Abstract 272: Reduced Uterine Perfusion Pressure Stimulated T-helper 17 Cells Cause Hypertension during Pregnancy
Preeclampsia (PE), new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and an imbalance among T-helper cell subtypes. Adoptive transfer of all CD4+ T cells from Reduced Uterine Perfusion Pressure (RUPP) rats into Normal Pregnant (NP) rats caused elevations in blood pressure and Angiotensin II type I receptor autoantibody (AT1-AA) and inflammatory cytokines. We have shown that chronic IL-17 infusion increases blood pressure and AT1-AA during pregnancy. Furthermore, we have shown that blockade of IL-17 decreases blood pressure and AT1-AA in the RUPP rat model of PE. The objective of this study was to determine a role for the elevated autoimmune associated T-helper 17 (TH17) cells from RUPP rats to cause hypertension and chronic inflammation during pregnancy. CD4+ CD25- Tcells were isolated from RUPP rat spleens using biotinylated antibody. Isolated cells were then stimulated on CD3 and CD28 magnetic beads and cultured in T-helper media to differentiate cells into TH17 cells. Differentiation of isolated cells into TH17 cells was verified via flow cytometry. On day 12 of gestation, 1x106 TH17 cells from RUPP rats were adoptively transferred into NP rats. Carotid catheters were inserted on gestation day18, and on day 19 blood pressure (MAP) was recorded, serum and plasma were collected. One-way ANOVA was used for statistical analysis. MAP increased from 99 ±2 mmHg in NP (n=8), to 128±4 mmHg in RUPP (n=9, P<0.0001). Likewise, adoptive transfer of RUPP TH17 cell into NP (NP + RUPP TH17) significantly increased MAP to 111±3 mmHg (n=11, P<0.001 compared to NP). AT1-AA significantly increased from 0.1±0.2 beats/min in NP to 15.6±0.7 beats/min in NP + RUPP TH17 rats (p<0.01). Plasma inflammatory cytokines were assessed via ELISA. IL-6 increased from 27.5±7.3 pg/mL in NP to 60.3±9.5 pg/mL in NP + RUPP TH17 rats (p<0.05); TNF-α increased from 11.4±9 pg/mL in NP to 19.9±6 pg/mL in NP + RUPP TH17; IL-17increased from 0.49±0.32 pg/ml in NP to 5.46±5 pg/mL in NP +RUPP TH17. In conclusion, RUPP TH17 cells increased blood pressure, AT1-AA, and inflammatory cytokines when transferred to NP rats, indicating a role for autoimmune associated TH17 cells, to cause much of the pathophysiology associated with PE.
- © 2013 by American Heart Association, Inc.