Heart disease is an integral part of Friedreich ataxia (FA). In addition to cardiomyocytes getting bigger, death of muscle fibers, and inflammatory infiltration, heart tissues show fibrosis and disorganized capillaries. This group examined the left ventricular wall (LVW) of 41 homozygous and 2 compound heterozygous FA patients aged 10-87 and 21 controls aged 2-69. They quantified the numbers of capillaries for comparison with the number of cardiac cells in the same field. The median ratio of capillaries to cardiomyocytes in samples from unaffected individuals was 1.0. In FA, the number of cardiomyocytes/mm² was significantly less, and the median ratio of capillaries to heart fibers was 2.0. There was a significant correlation of the expanded guanine-adenine-adenine trinucleotides (shorter allele, GAA1) with a younger age of onset, shorter disease duration, and lower cardiomyocyte counts. The ratio of capillaries to heart fibers was higher in patients with long GAA1 repeat expansions. Data supports endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis in FA. We propose that the pathogenesis of FA heart disease includes primary fibrosis.
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