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dc.contributor.author
Corral, Ricardo Santiago
dc.contributor.author
Santamaría, Miguel H.
dc.contributor.author
Corral, Ricardo Santiago
dc.date.available
2021-04-22T13:47:42Z
dc.date.issued
2018-01
dc.identifier.citation
Corral, Ricardo Santiago; Santamaría, Miguel H.; Corral, Ricardo Santiago; Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1864; 1; 1-2018; 11-23
dc.identifier.issn
0925-4439
dc.identifier.uri
http://hdl.handle.net/11336/130714
dc.description.abstract
Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 −/−) mice were parasite-infected (Brazil strain) for 100 days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 −/− infection showed lower heart-to-body ratio (P < 0.01) as well as reduced inflammatory pathology (P < 0.05), CCL5 expression (P < 0.05), myocyte size (P < 0.05) and fibrosis (P < 0.01) in cardiac tissues. Intense OPN labeling was observed in inflammatory cells recruited to infected heart (P < 0.05). Plasma concentration of MMP-2 was higher (P < 0.05) in infected WT than in spp1 −/− mice. Coincidently, specific immunostaining revealed increased gelatinase expression (P < 0.01) and activity (P < 0.05) in the inflamed hearts from T. cruzi WT mice, but not in their spp1 −/− littermates. CCL5 and MMP-2 induction occurred preferentially (P < 0.01) in WT heart-invading CD8+ T cells and was mediated via phospho-JNK MAPK signaling. Heart levels of OPN, CCL5 and MMP-2 correlated (P < 0.01) with collagen accumulation in the infected WT group only. Endogenous OPN emerges as a key player in the pathogenesis of chronic Chagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro-inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CARDIAC REMODELING
dc.subject
CHAGAS CARDIOMYOPATHY
dc.subject
INFLAMMATION
dc.subject
OSTEOPONTIN
dc.subject
TRYPANOSOMA CRUZI
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-21T18:57:12Z
dc.journal.volume
1864
dc.journal.number
1
dc.journal.pagination
11-23
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Corral, Ricardo Santiago. Centro de Estudios Metabólicos; España. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
dc.description.fil
Fil: Santamaría, Miguel H.. Centro de Estudios Metabólicos; España
dc.description.fil
Fil: Corral, Ricardo Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Biochimica et Biophysica Acta - Molecular Basis of Disease
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0925443917303617?via%3Dihub
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbadis.2017.10.006
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