title: CD4+ T cells are important mediators of oxidative stress that cause hypertension in response to placental ischemia.
abstract: 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.
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Cornelius
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Scott
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Judith
authors.initials: J
authors.lastname: Heath
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Janae
authors.initials: J
authors.lastname: Moseley
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Krystal
authors.initials: K
authors.lastname: Chatman
authors.affiliation: From the Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular-Renal Research (K.W., J.H., K.C.) and Department of Pharmacology and Toxicology (D.C.C., J.S., J.M., B.L.), University of Mississippi Medical Center, Jackson. bblamarca@umc.edu.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control; D007511:Ischemia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010920:Placenta / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000503:physiopathology* / Q000517:prevention & control; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D017382:Reactive Oxygen Species; C056165:acetovanillone; D009195:Peroxidase
keywords: hypertension; oxidative stress; preeclampsia