Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes. Physiol Rep 2015 Jan 01;3(1)
Date
01/21/2015Pubmed ID
25602015Pubmed Central ID
PMC4387753DOI
10.14814/phy2.12257Scopus ID
2-s2.0-84992329274 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
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 CDAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinCurt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
