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Myocardial Alterations in the Murine Model of Fabry Disease Can Be Reversed by Enzyme Replacement Therapy.
MedLine Citation:
PMID:  21477968     Owner:  NLM     Status:  Publisher    
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 < .05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < .05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < .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 < .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.
Paula A Rozenfeld; Mariana Fritz; Paula Blanco; Pedro Gonzalez; Gustavo J Rinaldi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-6
Journal Detail:
Title:  The Canadian journal of cardiology     Volume:  -     ISSN:  1916-7075     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8510280     Medline TA:  Can J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Facultad de Ciencias Exactas, Departamento de Ciencias Biológicas, Universidad Nacional de La Plata, La Plata, Argentina; LISIN, Facultad de Ciencias Exactas, Departamento de Ciencias Biológicas, Universidad Nacional de La Plata, La Plata, Argentina.
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