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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Periodicals, Inc.
2015
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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 |
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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 |
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