Journal article
Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
Physiological Reports, Vol.3(1), pp.e12257-n/a
2015
DOI: 10.14814/phy2.12257
PMCID: PMC4387753
PMID: 25602015
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. Indoleamine 2,3 Dioxygenase (IDO) has been implicated in the T‐cell dysregulation and early pathogenesis of the devastating pregnancy‐related hypertensive disease, preeclampsia. We demonstrate that chronic deficiency in IDO in a IDO‐KO mouse model recapitulates many of the essential phenotypes of human preeclampsia including renal damage. This novel model will help dissect the role of IDO and T cells in the early pathogenesis of preeclampsia.
Details
- Title: Subtitle
- Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
- Creators
- Mark K Santillan - The Center for Hypertension Research, University of IowaChristopher J Pelham - Department of Pharmacology, University of IowaPimonrat Ketsawatsomkron - Department of Pharmacology, University of IowaDonna A Santillan - The Center for Hypertension Research, University of IowaDeborah R Davis - Department of Pharmacology, University of IowaEric J Devor - Department of Obstetrics & Gynecology, University of IowaKatherine N Gibson‐Corley - Department of Pathology, University of IowaSabrina M Scroggins - Department of Obstetrics & Gynecology, University of IowaJustin L Grobe - Department of Pharmacology, University of IowaBaoli Yang - Department of Obstetrics & Gynecology, University of IowaSteven K Hunter - Department of Obstetrics & Gynecology, University of IowaCurt D Sigmund - Department of Pharmacology, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Physiological Reports, Vol.3(1), pp.e12257-n/a
- DOI
- 10.14814/phy2.12257
- PMID
- 25602015
- PMCID
- PMC4387753
- NLM abbreviation
- Physiol Rep
- ISSN
- 2051-817X
- eISSN
- 2051-817X
- Publisher
- Wiley Periodicals, Inc
- Grant note
- name: University of Iowa Center for Hypertension Research; DOI: 10.13039/100000002, name: National Institutes of Health, award: HD000849, RR024980, HL098276, HL084207, KL2 TR000444; DOI: 10.13039/100000968, name: American Heart Association, award: 14IRG1871001; name: University of Iowa Carver Trust
- Language
- English
- Date published
- 2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pathology; Obstetrics and Gynecology; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9983931816702771
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