The role of connexin 43 in remodeling cardiomyocyte intercellular contacts in hypertrophic cardiomyopathy

Abstract

BACKGROUND: Intercellular gap junctions play a special role in the biology of cellular interactions. Their structural and dispositional changes can affect some biological functions, including disruption of electrical pulse propagation, which is primarily important for myocardial function.

AIM: The aim was to evaluate the morphological characteristics and localization of connexin 43-containing (Cx43⁺) gap — junctions and to determine their association with changes in myocardial morphology of the interventricular septum and clinical parameters in patients with hypertrophic cardiomyopathy.

MATERIALS AND METHODS: Morphometry and immunohistochemistry of interventricular septal myocardium were performed in patients with hypertrophic cardiomyopathy (n = 62, aged 18 to 61 years) compared with subjects without cardiovascular disease (n = 8, aged 25 to 54 years). Resection of the interventricular septum of the right ventricle was performed in patients with hypertrophic cardiomyopathy. Cx43⁺ gap junctions were identified in cardiomyocytes and their location and ultrastructural arrangement were determined. The data obtained were compared with clinical parameters of patients with hypertrophic cardiomyopathy.

RESULTS: In the interventricular septal myocardium of patients with hypertrophic cardiomyopathy, a redistribution of Cx43+ gap junctions from intercalated discs to the lateral surfaces of cardiomyocytes was observed. Gap junction changes are more frequent and more extensive in patients with hypertrophic cardiomyopathy than in the control group. They are typical of patients with the most severe morphological and functional cardiac condition, as evidenced by echocardiographic data such as significant thickening of the interventricular septum and a decrease in the volume of the left ventricular cavity. Morphologically complex remodeling of the myocardium is manifested by hypertrophy of the cardiomyocytes and partial loss of their myofibrils. Ultrastructurally, 28.1% of patients with hypertrophic cardiomyopathy had gap junction defects in the myocardium such as sites of localized divergence of intercalated disc membranes and abnormal ring structures formed by invaginations of gap junction-containing sarcolemma.

CONCLUSION: The location of Cx43⁺ gap junctions on the lateral surfaces of cardiomyocytes and changes in their ultrastructure suggest cardiomyocyte immaturity of the interventricular septum, which is typical of patients with hypertrophic cardiomyopathy and may cause a disruption of the electromechanical coupling of the myocardium.

Keywords

hypertrophic cardiomyopathy / cardiomyocytes / intercellular interactions / gap junctions / connexin 43

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Funding

Government of the Russian FederationПравительство Российской ФедерацииGovernment of the Russian Federation(123030700104-3)

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