Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy

Autores
Rozenfeld, Paula Adriana; Fritz, Mariana; Blanco, Paula Graciela; Gonzalez, Pedro; Rinaldi, Gustavo Juan
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Fabry disease results from deficiency of alpha-galactosidase A (AGA), causing lysosomal storage of globotriaosylceramide in heart and other tissues. Since 2003, enzymatic replacement therapy with recombinant AGA agalsidase alfa (R-AGA) was approved for clinical use. Methods: We evaluated whether, in mice knocked out for AGA (FM, n = 31), the myocardium was altered with respect to the wild-type mice (WT, n = 25) and whether alterations were reversed in FM treated with intravenous R-AGA, 0.5 mg/kg every other week during 2 months (FM-AGA, n = 12). Results: Left ventricular (LV) contractility was depressed in FM, evaluated by LV ΔP/Δt (FM = 2832 ± 85 mm Hg/s, WT = 3179 ± 119 mm Hg/s; P < 0.05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < 0.05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < 0.05). LV stiffness (arrested hearts) decreased in FM (FM=35.57± 3.5 mm Hg/20 μl; WT = 68.86 ± 6.12 mm Hg/20 μl; P < 0.05). FM myocytes showed augmented size, disorganized architecture, and intracytoplasmic vacuolization. Alterations reverted in FM-AGA: LV ΔP/Δt = 3281 ± 456 mm Hg/s and LV stiffness = 58.83 ± 2.15 mm Hg/20 μl, with normalization of myocyte architecture. No reversion was detected with AGA solvent. Conclusions: The FM represent a mild, early stage of the disease, since myocardial alterations are not prominent and appear in nonhypertrophic hearts. Reversion of alterations in the FM-AGA suggests that enzymatic replacement therapy can be useful when administered in early stages of this disease.
Fil: Rozenfeld, Paula Adriana. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fritz, Mariana. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Gonzalez, Pedro. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Rinaldi, Gustavo Juan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Materia
Myocardium
Murine
Fabry disease
Enzyme replacement therapy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/95872
Acceder
id CONICETDig_cb6d18f6f49581a7fefd3fb845e98061
oai_identifier_str oai:ri.conicet.gov.ar:11336/95872
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement TherapyRozenfeld, Paula AdrianaFritz, MarianaBlanco, Paula GracielaGonzalez, PedroRinaldi, Gustavo JuanMyocardiumMurineFabry diseaseEnzyme replacement therapyhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Fabry disease results from deficiency of alpha-galactosidase A (AGA), causing lysosomal storage of globotriaosylceramide in heart and other tissues. Since 2003, enzymatic replacement therapy with recombinant AGA agalsidase alfa (R-AGA) was approved for clinical use. Methods: We evaluated whether, in mice knocked out for AGA (FM, n = 31), the myocardium was altered with respect to the wild-type mice (WT, n = 25) and whether alterations were reversed in FM treated with intravenous R-AGA, 0.5 mg/kg every other week during 2 months (FM-AGA, n = 12). Results: Left ventricular (LV) contractility was depressed in FM, evaluated by LV ΔP/Δt (FM = 2832 ± 85 mm Hg/s, WT = 3179 ± 119 mm Hg/s; P < 0.05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < 0.05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < 0.05). LV stiffness (arrested hearts) decreased in FM (FM=35.57± 3.5 mm Hg/20 μl; WT = 68.86 ± 6.12 mm Hg/20 μl; P < 0.05). FM myocytes showed augmented size, disorganized architecture, and intracytoplasmic vacuolization. Alterations reverted in FM-AGA: LV ΔP/Δt = 3281 ± 456 mm Hg/s and LV stiffness = 58.83 ± 2.15 mm Hg/20 μl, with normalization of myocyte architecture. No reversion was detected with AGA solvent. Conclusions: The FM represent a mild, early stage of the disease, since myocardial alterations are not prominent and appear in nonhypertrophic hearts. Reversion of alterations in the FM-AGA suggests that enzymatic replacement therapy can be useful when administered in early stages of this disease.Fil: Rozenfeld, Paula Adriana. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fritz, Mariana. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blanco, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Gonzalez, Pedro. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Rinaldi, Gustavo Juan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaPulsus Group Inc2011-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95872Rozenfeld, Paula Adriana; Fritz, Mariana; Blanco, Paula Graciela; Gonzalez, Pedro; Rinaldi, Gustavo Juan; Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy; Pulsus Group Inc; Canadian Journal Of Cardiology; 27; 3; 5-2011; 339-3450828-282XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0828282X10000516info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cjca.2010.12.035info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:51Zoai:ri.conicet.gov.ar:11336/95872instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:51.658CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
title Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
spellingShingle Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
Rozenfeld, Paula Adriana
Myocardium
Murine
Fabry disease
Enzyme replacement therapy
title_short Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
title_full Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
title_fullStr Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
title_full_unstemmed Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
title_sort Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy
dc.creator.none.fl_str_mv Rozenfeld, Paula Adriana
Fritz, Mariana
Blanco, Paula Graciela
Gonzalez, Pedro
Rinaldi, Gustavo Juan
author Rozenfeld, Paula Adriana
author_facet Rozenfeld, Paula Adriana
Fritz, Mariana
Blanco, Paula Graciela
Gonzalez, Pedro
Rinaldi, Gustavo Juan
author_role author
author2 Fritz, Mariana
Blanco, Paula Graciela
Gonzalez, Pedro
Rinaldi, Gustavo Juan
author2_role author
author
author
author
dc.subject.none.fl_str_mv Myocardium
Murine
Fabry disease
Enzyme replacement therapy
topic Myocardium
Murine
Fabry disease
Enzyme replacement therapy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Fabry disease results from deficiency of alpha-galactosidase A (AGA), causing lysosomal storage of globotriaosylceramide in heart and other tissues. Since 2003, enzymatic replacement therapy with recombinant AGA agalsidase alfa (R-AGA) was approved for clinical use. Methods: We evaluated whether, in mice knocked out for AGA (FM, n = 31), the myocardium was altered with respect to the wild-type mice (WT, n = 25) and whether alterations were reversed in FM treated with intravenous R-AGA, 0.5 mg/kg every other week during 2 months (FM-AGA, n = 12). Results: Left ventricular (LV) contractility was depressed in FM, evaluated by LV ΔP/Δt (FM = 2832 ± 85 mm Hg/s, WT = 3179 ± 119 mm Hg/s; P < 0.05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < 0.05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < 0.05). LV stiffness (arrested hearts) decreased in FM (FM=35.57± 3.5 mm Hg/20 μl; WT = 68.86 ± 6.12 mm Hg/20 μl; P < 0.05). FM myocytes showed augmented size, disorganized architecture, and intracytoplasmic vacuolization. Alterations reverted in FM-AGA: LV ΔP/Δt = 3281 ± 456 mm Hg/s and LV stiffness = 58.83 ± 2.15 mm Hg/20 μl, with normalization of myocyte architecture. No reversion was detected with AGA solvent. Conclusions: The FM represent a mild, early stage of the disease, since myocardial alterations are not prominent and appear in nonhypertrophic hearts. Reversion of alterations in the FM-AGA suggests that enzymatic replacement therapy can be useful when administered in early stages of this disease.
Fil: Rozenfeld, Paula Adriana. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fritz, Mariana. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Gonzalez, Pedro. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Rinaldi, Gustavo Juan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
description Background: Fabry disease results from deficiency of alpha-galactosidase A (AGA), causing lysosomal storage of globotriaosylceramide in heart and other tissues. Since 2003, enzymatic replacement therapy with recombinant AGA agalsidase alfa (R-AGA) was approved for clinical use. Methods: We evaluated whether, in mice knocked out for AGA (FM, n = 31), the myocardium was altered with respect to the wild-type mice (WT, n = 25) and whether alterations were reversed in FM treated with intravenous R-AGA, 0.5 mg/kg every other week during 2 months (FM-AGA, n = 12). Results: Left ventricular (LV) contractility was depressed in FM, evaluated by LV ΔP/Δt (FM = 2832 ± 85 mm Hg/s, WT = 3179 ± 119 mm Hg/s; P < 0.05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < 0.05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < 0.05). LV stiffness (arrested hearts) decreased in FM (FM=35.57± 3.5 mm Hg/20 μl; WT = 68.86 ± 6.12 mm Hg/20 μl; P < 0.05). FM myocytes showed augmented size, disorganized architecture, and intracytoplasmic vacuolization. Alterations reverted in FM-AGA: LV ΔP/Δt = 3281 ± 456 mm Hg/s and LV stiffness = 58.83 ± 2.15 mm Hg/20 μl, with normalization of myocyte architecture. No reversion was detected with AGA solvent. Conclusions: The FM represent a mild, early stage of the disease, since myocardial alterations are not prominent and appear in nonhypertrophic hearts. Reversion of alterations in the FM-AGA suggests that enzymatic replacement therapy can be useful when administered in early stages of this disease.
publishDate 2011
dc.date.none.fl_str_mv 2011-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/95872
Rozenfeld, Paula Adriana; Fritz, Mariana; Blanco, Paula Graciela; Gonzalez, Pedro; Rinaldi, Gustavo Juan; Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy; Pulsus Group Inc; Canadian Journal Of Cardiology; 27; 3; 5-2011; 339-345
0828-282X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95872
identifier_str_mv Rozenfeld, Paula Adriana; Fritz, Mariana; Blanco, Paula Graciela; Gonzalez, Pedro; Rinaldi, Gustavo Juan; Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy; Pulsus Group Inc; Canadian Journal Of Cardiology; 27; 3; 5-2011; 339-345
0828-282X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0828282X10000516
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cjca.2010.12.035
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pulsus Group Inc
publisher.none.fl_str_mv Pulsus Group Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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