title: Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes.
abstract: Preeclampsia is a cardiovascular disorder of late pregnancy that is, commonly characterized by hypertension, renal structural damage and dysfunction, and fetal growth restriction. Prevailing etiologic models of this disorder include T-cell dysfunction as an initiating cause of preeclampsia. Indoleamine 2,3-dioxygenase (IDO), an enzyme that mediates the conversion of tryptophan to kynurenine, has been linked to preeclampsia in humans, and is known to regulate T-cell activity and an endothelial-derived relaxing factor. To test the hypothesis that IDO is causally involved in the pathogenesis of preeclampsia, mice deficient for IDO (IDO-KO) were generated on a C57BL/6 background. IDO-KO and wild-type C57BL/6 mice were bred, and preeclampsia phenotypes were evaluated during pregnancy. Pregnant IDO-KO mice exhibited pathognomonic renal glomerular endotheliosis, proteinuria, pregnancy-specific endothelial dysfunction, intrauterine growth restriction, and mildly elevated blood pressure compared to wild-type mice. Together these findings highlight an important role for IDO in the generation of phenotypes typical of preeclampsia. Loss of IDO function may represent a risk factor for the development of preeclampsia. By extension, increased IDO activity, reductions in IDO reactants, or increases in IDO products may represent novel therapeutic approaches for this disorder.
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa The Center for Hypertension Research, University of Iowa, Iowa City, Iowa.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Santillan
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pelham
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Pimonrat
authors.initials: P
authors.lastname: Ketsawatsomkron
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa The Center for Hypertension Research, University of Iowa, Iowa City, Iowa.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Santillan
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Davis
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Devor
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, Iowa.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Gibson-Corley
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa.
authors.forename: Sabrina M
authors.initials: SM
authors.lastname: Scroggins
authors.affiliation: The Center for Hypertension Research, University of Iowa, Iowa City, Iowa Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa.
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa, Iowa City, Iowa.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Hunter
authors.affiliation: The Center for Hypertension Research, University of Iowa, Iowa City, Iowa Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
keywords: Animal model; T cell; indoleamine 2,3‐dioxygenase; preeclampsia