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Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes. Physiol Rep 2015 Jan 01;3(1)

Date

01/21/2015

Pubmed ID

25602015

Pubmed Central ID

PMC4387753

DOI

10.14814/phy2.12257

Scopus ID

2-s2.0-84992329274   40 Citations

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.

Author List

Santillan MK, Pelham CJ, Ketsawatsomkron P, Santillan DA, Davis DR, Devor EJ, Gibson-Corley KN, Scroggins SM, Grobe JL, Yang B, Hunter SK, Sigmund CD

Authors

Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin