Ultrastructural changes in myocardial cells of mice with dysferlinopathy (Bla/J line)

Abstract

BACKGROUND: Striated cardiac muscle tissue in dysferlinopathy, a rare hereditary muscular dystrophy, has been the subject of limited research. Dysferlinopathy is traditionally considered a disease that predominantly affects skeletal muscles, as clinically significant heart failure is rare in affected individuals. However, myocardial involvement due to hereditary dysferlin deficiency has been described in only a few studies. The development of heart failure in these patients may result from both circulatory remodeling due to hypodynamia and direct myocardial damage. Structural changes observed in Bla/J mice with dysferlinopathy provide evidence for direct myocardial damage. However, submicroscopic alterations in cardiomyocytes and stromal myocardial cells (fibroblasts, endothelial cells, telocytes), as well as their role in the pathomorphogenesis of dysferlinopathy, remain insufficiently studied.

AIM: To characterize the ultrastructure of cardiomyocytes and stromal myocardial cells in the left ventricle of dysferlin-deficient Bla/J mice.

METHODS: Myocardial left ventricle fragments from Bla/J and C57BL/6 (control group) mice at 3, 6, 9, and 12 months of age were fixed and embedded in Araldite resin. Ultrathin sections (50–100 nm) were prepared, stained using Reynolds’ method, and examined via transmission electron microscopy.

RESULTS: Ultrastructural changes in the myocardium of Bla/J dysferlin-deficient mice included: destruction of the sarcolemma and intercalated discs; expansion and vacuolization of the sarcoplasmic reticulum; mitochondrial polymorphism. Additionally, myelin-like structures were detected in subsarcolemmal spaces and sarcoplasmic reticulum cisterns. In dysferlin-deficient mice, telocytes exhibited signs of degeneration. In contrast, the control group (C57BL/6 mice) showed no significant ultrastructural changes.

CONCLUSION: Ultrastructural evidence of myocardial damage in dysferlin-deficient Bla/J mice suggests a potential role of dysferlin in maintaining the structural integrity of cardiomyocytes and stromal cells.

Keywords

dysferlinopathy / DYSF / striated cardiac muscle tissue / transmission electron microscopy / telocytes

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Funding

Ministry of Science and Higher Education of the Russian FederationМинистерство науки и высшего образования Российской Федерации俄羅斯聯邦科學與高等教育部(075-15-2021-1346)

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