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An increased population of regulatory T cells improves the pathophysiology of placental ischemia in a rat model of preeclampsia

Item Type:Article
Title:An increased population of regulatory T cells improves the pathophysiology of placental ischemia in a rat model of preeclampsia
Creators Name:Cornelius, D.C. and Amaral, L.M. and Harmon, A. and Wallace, K. and Thomas, A.J. and Campbell, N. and Scott, J. and Herse, F. and Haase, N. and Moseley, J. and Wallukat, G. and Dechend, R. and LaMarca, B.
Abstract:The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits much of the pathology characterizing this disease, such as hypertension, inflammation, suppressed regulatory T cells (TRegs), reactive oxygen species (ROS), and autoantibodies to the ANG II type I receptor (AT1-AA) during pregnancy. The objective of this study was to determine whether supplementation of normal pregnant (NP) TRegs into RUPP rats would attenuate the pathophysiology associated with preeclampsia during pregnancy. CD4(+)/CD25(+) T cells were isolated from spleens of NP and RUPP rats, cultured, and injected into gestation day (GD) 12 normal pregnant rats that underwent the RUPP procedure on GD 14. On GD 1, mean arterial pressure (MAP) was recorded, and blood and tissues were collected for analysis. One-way ANOVA was used for statistical analysis. MAP increased from 99 +/- 2 mmHg in NP (n = 12) to 127 +/- 2 mmHg in RUPP (n = 21) but decreased to 118 +/- 2 mmHg in RUPP+NP TRegs (n = 17). Circulating IL-6 and IL-10 were not significantly changed, while circulating TNF-alpha and IL-17 were significantly decreased after supplementation of TRegs. Placental and renal ROS were 339 +/- 58.7 and 603 +/- 88.1 RLU.min(-1).mg(-1) in RUPP and significantly decreased to 178 +/- 27.8 and 171 +/- 55.6 RLU.min(-1).mg(-1), respectively, in RUPP+NP TRegs; AT1-AA was 17.81 +/- 1.1 beats per minute (bpm) in RUPP but was attenuated to 0.50 +/- 0.3 bpm with NP TRegs. This study demonstrates that NP TRegs can significantly improve inflammatory mediators, such as IL-17, TNF-alpha, and AT1-AA, which have been shown to increase blood pressure during pregnancy.
Keywords:Hypertension, Pregnancy, Inflammation, Oxidative Stress, Regulatory T Cells, Animals, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society (U.S.A.)
Volume:309
Number:8
Page Range:R884-R891
Date:15 October 2015
Official Publication:https://doi.org/10.1152/ajpregu.00154.2015
PubMed:View item in PubMed

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