Changes in the pathomorphological condition of the myocardium in dysferlinopathy mice (Bla/J type)

Abstract

BACKGROUND:Dysferlinopathy is heritable progressive muscular dystrophy caused byDYSFmutation. Currently, although skeletal muscle pathology has been defined, only fragmentary and limited myocardium histopathology data are available. AIM:The study aimed to analyze the pathomorphological status of the myocardium in Bla/J mice models of dysferlinopathy at different ages. MATERIALS AND METHODS:Data from two experimental groups were analyzed: Bla/J mice withDYSFknockout on 3, 6, and 12 months old and control wild-type Balb/C mice aged 6 months. The expressions and patterns of dyeing of protein dysferlin in the immunofluorescent search method were analyzed. These were held such parameters of the histological characteristic of the myocardium of three dyeing protocols (hematoxylin and eosin, iron hematoxylin by Rego, and hematoxylin-basic fuchsin-picric acid by Lie), and morphometry of the parameters of the cardiomyocytes (length, width of cardiomyocytes, and nuclear perimeter). RESULTS:The immunofluorescent search method revealed high levels of dysferlin in the myocardium of the control group. Statistical analysis showed significant differences between Bla/J and Balb/C mice: the increasing length and width of cardiomyocytes in dysferlinopathy by 49.9% ((95% confidence interval, 45.9–57.4) and 35.6 (95% confidence interval, 32.9–37.9)), respectively. Nucleus perimeter was significantly reduced in the dysferlinopathy group with disease duration of 6 months (by 23.9 (95% confidence interval, 20.2–27.5) compared with the group with disease duration of 3 months and by 18.8% (95% confidence interval, 8.5–19.7)) and the control group. Consequently, progressive hypertrophy of cardiomyocytes, increasing deformation in cardiomyocytes, intercalated disk destruction, hypoxia features, and necrosis indication were observed, resulting in fibrosis. A pattern of cardiomyocyte size reduction dependent on the aging process was observed. CONCLUSIONS:Dysferlin deficiency leads to significant damage in the myocardium of Bla/J mice.