Cargando…

Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes

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. Indoleam...

Descripción completa

Detalles Bibliográficos
Autores principales: Santillan, Mark K., Pelham, Christopher J., Ketsawatsomkron, Pimonrat, Santillan, Donna A., Davis, Deborah R., Devor, Eric J., Gibson‐Corley, Katherine N., Scroggins, Sabrina M., Grobe, Justin L., Yang, Baoli, Hunter, Steven K., Sigmund, Curt D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Periodicals, Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387753/
https://www.ncbi.nlm.nih.gov/pubmed/25602015
http://dx.doi.org/10.14814/phy2.12257
_version_ 1782365318778191872
author Santillan, Mark K.
Pelham, Christopher J.
Ketsawatsomkron, Pimonrat
Santillan, Donna A.
Davis, Deborah R.
Devor, Eric J.
Gibson‐Corley, Katherine N.
Scroggins, Sabrina M.
Grobe, Justin L.
Yang, Baoli
Hunter, Steven K.
Sigmund, Curt D.
author_facet Santillan, Mark K.
Pelham, Christopher J.
Ketsawatsomkron, Pimonrat
Santillan, Donna A.
Davis, Deborah R.
Devor, Eric J.
Gibson‐Corley, Katherine N.
Scroggins, Sabrina M.
Grobe, Justin L.
Yang, Baoli
Hunter, Steven K.
Sigmund, Curt D.
author_sort Santillan, Mark K.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4387753
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Wiley Periodicals, Inc.
record_format MEDLINE/PubMed
spelling pubmed-43877532015-04-13 Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes Santillan, Mark K. Pelham, Christopher J. Ketsawatsomkron, Pimonrat Santillan, Donna A. Davis, Deborah R. Devor, Eric J. Gibson‐Corley, Katherine N. Scroggins, Sabrina M. Grobe, Justin L. Yang, Baoli Hunter, Steven K. Sigmund, Curt D. Physiol Rep Original Research 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. Wiley Periodicals, Inc. 2015-01-19 /pmc/articles/PMC4387753/ /pubmed/25602015 http://dx.doi.org/10.14814/phy2.12257 Text en © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Santillan, Mark K.
Pelham, Christopher J.
Ketsawatsomkron, Pimonrat
Santillan, Donna A.
Davis, Deborah R.
Devor, Eric J.
Gibson‐Corley, Katherine N.
Scroggins, Sabrina M.
Grobe, Justin L.
Yang, Baoli
Hunter, Steven K.
Sigmund, Curt D.
Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title_full Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title_fullStr Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title_full_unstemmed Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title_short Pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
title_sort pregnant mice lacking indoleamine 2,3‐dioxygenase exhibit preeclampsia phenotypes
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387753/
https://www.ncbi.nlm.nih.gov/pubmed/25602015
http://dx.doi.org/10.14814/phy2.12257
work_keys_str_mv AT santillanmarkk pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT pelhamchristopherj pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT ketsawatsomkronpimonrat pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT santillandonnaa pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT davisdeborahr pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT devorericj pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT gibsoncorleykatherinen pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT scrogginssabrinam pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT grobejustinl pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT yangbaoli pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT hunterstevenk pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes
AT sigmundcurtd pregnantmicelackingindoleamine23dioxygenaseexhibitpreeclampsiaphenotypes