CD4+ T Cells Are Important Mediators of Oxidative Stress That Cause Hypertension in Response to Placental Ischemia
Preeclampsia is associated with oxidative stress, which is suspected to play a role in hypertension, placental ischemia, and fetal demise associated with the disease. Various cellular sources of oxidative stress, such as neutrophils, monocytes, and CD4+ T cells have been suggested as culprits in the pathophysiology of preeclampsia. The objective of this study was to examine a role of circulating and placental CD4+ T cells in oxidative stress in response to placental ischemia during pregnancy. CD4+ T cells and oxidative stress were measured in preeclamptic and normal pregnant women, placental ischemic and normal pregnant rats, and normal pregnant recipient rats of placental ischemic CD4+ T cells. Women with preeclampsia had significantly increased circulating (P=0.02) and placental CD4+ T cells (P=0.0001); lymphocyte secretion of myeloperoxidase (P=0.004); and placental reactive oxygen species (P=0.0004) when compared with normal pregnant women. CD4+ T cells from placental ischemic rats cause many facets of preeclampsia when injected into normal pregnant recipient rats on gestational day 13. On gestational day 19, blood pressure increased in normal pregnant recipients of placental ischemic CD4+ T cells (P=0.002) compared with that in normal pregnant rats. Similar to preeclamptic patients, CD4+ T cells from placental ischemic rats secreted significantly more myeloperoxidase (P=0.003) and induced oxidative stress in cultured vascular cells (P=0.003) than normal pregnant rat CD4+Tcells. Apocynin, a nicotinamide adenine dinucleotide phosphate inhibitor, attenuated hypertension and all oxidative stress markers in placental ischemic and normal pregnant recipient rats of placental ischemic CD4+Tcells (P=0.05). These data demonstrate an important role for CD4+ T cells in mediating another factor, oxidative stress, to cause hypertension during preeclampsia.
- Received March 20, 2014.
- Revision received April 13, 2014.
- Accepted July 11, 2014.
- © 2014 American Heart Association, Inc.