Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabol...

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Detalhes bibliográficos
Autores: Gironès, Núria, Carbajosa, Sofía, Guerrero, Néstor A., Poveda, Cristina, Chillón-Marinas, Carlos, Fresno, Manuel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/124626
Acesso em linha:http://hdl.handle.net/10261/124626
Access Level:acceso abierto
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spelling Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi InfectionGironès, NúriaCarbajosa, SofíaGuerrero, Néstor A.Poveda, CristinaChillón-Marinas, CarlosFresno, Manuel© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer ReviewedPublic Library of ScienceMinisterio de Ciencia e Innovación (España)Fundación Ramón ArecesMinisterio de Asuntos Exteriores y Cooperación (España)European CommissionUniversidad Autónoma de MadridComunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520142015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/124626reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1246262026-05-22T06:33:51Z
dc.title.none.fl_str_mv Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
title Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
spellingShingle Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
Gironès, Núria
title_short Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
title_full Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
title_fullStr Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
title_full_unstemmed Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
title_sort Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
dc.creator.none.fl_str_mv Gironès, Núria
Carbajosa, Sofía
Guerrero, Néstor A.
Poveda, Cristina
Chillón-Marinas, Carlos
Fresno, Manuel
author Gironès, Núria
author_facet Gironès, Núria
Carbajosa, Sofía
Guerrero, Néstor A.
Poveda, Cristina
Chillón-Marinas, Carlos
Fresno, Manuel
author_role author
author2 Carbajosa, Sofía
Guerrero, Néstor A.
Poveda, Cristina
Chillón-Marinas, Carlos
Fresno, Manuel
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Fundación Ramón Areces
Ministerio de Asuntos Exteriores y Cooperación (España)
European Commission
Universidad Autónoma de Madrid
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description © 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/124626
url http://hdl.handle.net/10261/124626
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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