ArticleJournal of the American Heart Association2025
Fabry Cardiomyopathy: Myocardial Fibrosis, Inflammation, and Down-Regulation of Mannose-6-Phosphate Receptors Cause Low Accessibility to Enzyme Replacement Therapy.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Review
- Endothelial dysfunction in Fabry disease: retinal biomarkers link cardiac GLA gene variants with chronic inflammation.NPJ genomic medicine · 2026Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe clinical impact of enzyme replacement therapy on advanced Fabry disease cardiomyopathy appears to be limited. The pathologic mechanisms involved are still unclear. METHODS AND
resultsTen male patients with advanced Fabry disease cardiomyopathy on enzyme replacement therapy, whose disease progressed from maximal wall thickness of 15.4±2.2 to 19.3±2.1 mm in 8.6±1.4 years of follow-up, underwent left ventricular endomyocardial biopsy before and 4 hours after β-agalsidase infusion (1 mg/kg). Comparative studies between pre- and postinfusion samples included the following: histology, electron microscopy and assessment of myocardial α-galactosidase A activity; immunohistochemistry for α-galactosidase A and semiquantitative evaluation (from 0 to 3) of its cardiomyocyte content; and ultrastructural immunogold analysis with anti-α-galactosidase A ab; and Western blot quantification of mannose-6-phosphate receptors. Controls were surgical biopsies from patients with mitral stenosis. Histologic and ultrastructural evaluation showed myocarditis in 7 of 10 patients, There was no removal of storage material while myocardial fibrosis was 9.8%±6.8% versus 3.8%±2.0% of controls. At ultrastructural immunogold analysis, myocardial α-galactosidase A activity increased in postinfusion samples by overall 1.89-fold. Alpha-galactosidase A immunostaining in cardiomyocytes was absent at baseline in all patients and did not significantly improve in postinfusion samples. Immunogold particles increased by 1.33-fold (17.6±3.6 preinfusion versus 21.5±5.9 postinfusion), remaining far from normal controls (86.9±6.6). Protein analysis showed mannose-6-phosphate receptors to be 81% lower than in a normal heart.
conclusionsIn spite of enzyme delivery to cardiac tissue, our study shows a low accessibility to enzyme replacement therapy of cardiomyocytes affected by advanced Fabry disease cardiomyopathy. It is sustained by myocardial fibrosis, inflammation, and severe down-regulation of mannose-6-phosphate receptors.
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