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Cardiac remodeling of intercalated discs in Friedreich's ataxia
Author(s) -
Mazurkiewicz Joseph E.,
Ramirez R. Lianne,
Koeppen Arnulf H.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1194.8
Subject(s) - frataxin , ataxia , intercalated disc , medicine , cardiology , ventricular remodeling , hypertrophic cardiomyopathy , heart failure , biology , neuroscience , microbiology and biotechnology , gap junction , intracellular , iron binding proteins , transferrin
Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by a defect in the gene for the mitochondrial protein frataxin, also displays cardiac involvement, most commonly as dilated cardiomyopathy and arrhythmia. Progression is related to the amount of residual frataxin and disease duration. Mechanical cardiomyocyte stress is very high in the left ventricular wall and may be responsible for the extensive scarring and remodeling of the myocardium. Such remodeling involves intercalated discs (ICD) that provide for mechanical cohesion between myocardial fibers and for impulse transmission through gap junctions (GJ). Altered distribution of GJ connexins (Cx) may lead to abnormal coupling between cardiomyocytes, contributing to arrhythmogenesis. Immunocytochemistry for N‐cadherin and CX43 were used to examine ICD structure and GJ distribution. In normal myocardium, N‐cadherin‐reactive ICD were distributed along cardiomyocytes at ~ equal distances of 40 μm. Fibers and ICD measured ~ 20 μm in dia. In FRDA, ICD appeared chaotic in their organization across hypertrophic fibers, with some fibers reaching 100 μm dia. “Lateralization” of CX43 in hypertrophic cardiomyocytes was prominent in FRDA. These findings in FRDA are consistent with similar features of cardiac remodeling in other diseases of the human heart. GJ and Cxs are increasingly suggested as potential therapeutic targets.