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| Item Type: | Article |
|---|---|
| Title: | CD4(+) T cells play a critical role in mediating hypertension in response to placental ischemia |
| Creators Name: | Novotny, S. and Wallace, K. and Herse, F. and Moseley, J. and Darby, M. and Heath, J. and Gill, J. and Wallukat, G. and Martin, J.N. and Dechend, R. and LaMarca, B. |
| Abstract: | Similar to preeclamptic women, hypertension in the chronic Reduced Uterine Perfusion Pressure Rat Model Of Preeclampsia (RUPP) is associated with increased CD4+ T cells, cytokines, sFlt-1 and agonistic autoantibodies to the AngII receptor (AT1-AA). We examined the effect inhibition of T cell co-stimulation in RUPP rats treated with (A) (abatacept, 250 mg/kg, infused i.v. at gestation day 13), on hypertension and sFlt-1, TNF-alpha and AT1-AA. RUPP surgical procedure was performed on day 14. On day 19 MAP increased from 94+2 mmHg in Normal Pregnant (NP) to 123 +/- 3 mmHg in RUPP control rats. This response was attenuated by Abatacept, MAP was 104 +/- 2 mmHg in RUPP +/- A, and 96 +/- 2 mmHg NP +/- A. Percent circulating CD4+ T cells were 66 +/- 3% in RUPPs compared to 55 +/- 3% NP rats (p<0.04) but were normalized in RUPP +/- A rats (54 +/- 3%). The twofold increase in TNF alpha seen in RUPPs (277 +/- 47 pg/ml) was decreased to 80 +/- 18 pg/ml in RUPP+A. Placental sFlt-1 was reduced 70 % to 151 +/- 28 in RUPP +/- A compared 488 +/- 61 pg/ml in RUPP (p<0.001). AT1-AA decreased from 20 +/- 0.8 bpm in control RUPP to 6 +/- 0.7 bpm in RUPP +/- A. We next determined the effect of RUPP in causing hypertension in pregnant T cell deficient rats by examining MAP in NP (123 +/- 5 mmHg) and RUPP athymic nude rats (123 +/- 7 mmHg). In the absence of T cells, hypertension in response to placental ischemia was completely abolished. Collectively these data indicate that CD4+ Tcells in response to placental ischemia play an important role in the pathophysiology of hypertension associated with preeclampsia. |
| Keywords: | Hypertension, Preeclampsia, Placental Ischemic Insult, Animals, Rats |
| Source: | Journal of Hypertension : Open Access |
| ISSN: | 2167-1095 |
| Publisher: | OMICS Publishing Group |
| Volume: | 2 |
| Page Range: | 116 |
| Date: | 17 June 2013 |
| Official Publication: | https://doi.org/10.4172/2167-1095.1000116 |
| PubMed: | View item in PubMed |
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