Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy

IntroductionChronic Chagasic Cardiomyopathy (CCC) has an infectious and inflammatory nature. Recent data also suggest an association with altered regulation of glucocorticoid (GC)-mediated circuits failing to control systemic inflammation. However, the involvement of glucocorticoid receptors (GR) an...

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Main Authors: Florencia B. González, Antonella Pacini, Araceli Castro, Susana Lioi, Silvina R. Villar, Luciano D’Attilio, Rodolfo D. Leiva, Liliana Favaloro, Oscar A. Bottasso, Carlos A. Vigliano, Ana Rosa Pérez
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Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1486772/full
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author Florencia B. González
Florencia B. González
Antonella Pacini
Araceli Castro
Susana Lioi
Silvina R. Villar
Silvina R. Villar
Luciano D’Attilio
Luciano D’Attilio
Rodolfo D. Leiva
Rodolfo D. Leiva
Liliana Favaloro
Oscar A. Bottasso
Oscar A. Bottasso
Carlos A. Vigliano
Carlos A. Vigliano
Ana Rosa Pérez
Ana Rosa Pérez
author_facet Florencia B. González
Florencia B. González
Antonella Pacini
Araceli Castro
Susana Lioi
Silvina R. Villar
Silvina R. Villar
Luciano D’Attilio
Luciano D’Attilio
Rodolfo D. Leiva
Rodolfo D. Leiva
Liliana Favaloro
Oscar A. Bottasso
Oscar A. Bottasso
Carlos A. Vigliano
Carlos A. Vigliano
Ana Rosa Pérez
Ana Rosa Pérez
author_sort Florencia B. González
collection DOAJ
description IntroductionChronic Chagasic Cardiomyopathy (CCC) has an infectious and inflammatory nature. Recent data also suggest an association with altered regulation of glucocorticoid (GC)-mediated circuits failing to control systemic inflammation. However, the involvement of glucocorticoid receptors (GR) and their isoforms have been unexplored.Materials and methodsThe expression of GR-α/β isoforms, 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), inflammatory cytokines, and the GC-regulated gene tristetraprolin (TTP) in peripheral blood mononuclear cells (PBMCs) as well as GR immunoreactivity in the myocardium from CCC individuals were evaluated by qPCR and immunohistochemistry respectively. Heart control samples with no evidence of structural heart disease and from ischemic cardiomyopathy patients were included. The presence of inflammatory infiltrates and fibrosis were also recorded.ResultsGR-α was expressed similarly in the PBMCs from Co and CCC individuals, but 11β-HSD1 expression was increased only in CCC, conjointly with enhanced ratios of IL-6/TTP and IFN-γ/TTP. In the inflamed myocardium from CCC patients, positive GR expression correlated with the intensity of the inflammatory infiltrate and cardiac hypertrophy.ConclusionThe infectious and inflammatory nature of CCC pathology seems strongly connected with the expression of GR in cardiac tissue samples, providing a stimulating background for further studies addressed to elucidate the influence of GR expression and function on CCC pathophysiology and cardiomyocyte hypertrophy.
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spelling doaj-art-b35f5859cc584a5d8f0644b228bd18a72025-01-30T05:10:05ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011610.3389/fendo.2025.14867721486772Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophyFlorencia B. González0Florencia B. González1Antonella Pacini2Araceli Castro3Susana Lioi4Silvina R. Villar5Silvina R. Villar6Luciano D’Attilio7Luciano D’Attilio8Rodolfo D. Leiva9Rodolfo D. Leiva10Liliana Favaloro11Oscar A. Bottasso12Oscar A. Bottasso13Carlos A. Vigliano14Carlos A. Vigliano15Ana Rosa Pérez16Ana Rosa Pérez17Instituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaInstituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaInstituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Buenos Aires, ArgentinaLaboratorio Central del Hospital Provincial del Centenario, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, ArgentinaInstituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaInstituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaServicio de Cardiología, Sección Chagas del Hospital Provincial del Centenario, Rosario, ArgentinaServicio de Insuficiencia Cardíaca y Trasplante Cardíaco, Hospital Universitario Fundación Favaloro, Buenos Aires, ArgentinaInstituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaInstituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Buenos Aires, ArgentinaServicio de Anatomía Patológica, Hospital Universitario de la Fundación Favaloro, Buenos Aires, ArgentinaInstituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario, ArgentinaFacultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, ArgentinaIntroductionChronic Chagasic Cardiomyopathy (CCC) has an infectious and inflammatory nature. Recent data also suggest an association with altered regulation of glucocorticoid (GC)-mediated circuits failing to control systemic inflammation. However, the involvement of glucocorticoid receptors (GR) and their isoforms have been unexplored.Materials and methodsThe expression of GR-α/β isoforms, 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), inflammatory cytokines, and the GC-regulated gene tristetraprolin (TTP) in peripheral blood mononuclear cells (PBMCs) as well as GR immunoreactivity in the myocardium from CCC individuals were evaluated by qPCR and immunohistochemistry respectively. Heart control samples with no evidence of structural heart disease and from ischemic cardiomyopathy patients were included. The presence of inflammatory infiltrates and fibrosis were also recorded.ResultsGR-α was expressed similarly in the PBMCs from Co and CCC individuals, but 11β-HSD1 expression was increased only in CCC, conjointly with enhanced ratios of IL-6/TTP and IFN-γ/TTP. In the inflamed myocardium from CCC patients, positive GR expression correlated with the intensity of the inflammatory infiltrate and cardiac hypertrophy.ConclusionThe infectious and inflammatory nature of CCC pathology seems strongly connected with the expression of GR in cardiac tissue samples, providing a stimulating background for further studies addressed to elucidate the influence of GR expression and function on CCC pathophysiology and cardiomyocyte hypertrophy.https://www.frontiersin.org/articles/10.3389/fendo.2025.1486772/fullglucocorticoid receptor11β-hydroxysteroid dehydrogenase type 1cardiomyocytehypertrophychronic chagasic cardiomyopathyischemic cardiomyopathy
spellingShingle Florencia B. González
Florencia B. González
Antonella Pacini
Araceli Castro
Susana Lioi
Silvina R. Villar
Silvina R. Villar
Luciano D’Attilio
Luciano D’Attilio
Rodolfo D. Leiva
Rodolfo D. Leiva
Liliana Favaloro
Oscar A. Bottasso
Oscar A. Bottasso
Carlos A. Vigliano
Carlos A. Vigliano
Ana Rosa Pérez
Ana Rosa Pérez
Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
Frontiers in Endocrinology
glucocorticoid receptor
11β-hydroxysteroid dehydrogenase type 1
cardiomyocyte
hypertrophy
chronic chagasic cardiomyopathy
ischemic cardiomyopathy
title Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
title_full Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
title_fullStr Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
title_full_unstemmed Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
title_short Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy
title_sort role of glucocorticoid receptor expression in chronic chagas cardiomyopathy implications for inflammation and cardiac hypertrophy
topic glucocorticoid receptor
11β-hydroxysteroid dehydrogenase type 1
cardiomyocyte
hypertrophy
chronic chagasic cardiomyopathy
ischemic cardiomyopathy
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1486772/full
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