Disruption of cell-cell adhesion in an inbred strain of hereditary cardiomyopathic hamster (Bio 14.6)

Abstract

Disarrangement of cardiomyocytes is a pathological characteristic of dilated cardiomyopathy. Hereditary cardiomyopathic hamster Bio 14.6, a model of dilated cardiomyopathy, displays disorder of cardiomyocyte arrangement. The aim of this study was to analyse the disturbance of cell alignment from the point of view of the cell-cell adhesion system in Bio 14.6. Cardiomyopathic hamster Bio 14.6 was used as a model of dilated cardiomyopathy. Histological study was performed by light and electron microscopy. Disorder of the adherens junction-specific cell-adhesion molecule (A-CAM) was analysed by immunofluorescent microscopy and immunoblotting with anti-A-CAM antibody. Hematoxylin-eosin staining revealed that intercalated disks were identifiable less clearly in cardiomyopathy than in a normal cardiac muscle. It was disclosed by electron microscopy that cardiomyocytes adhered to each other with reduction in subsarcolemmal electron density at intercalated disks in Bio 14.6 compared with normal hamsters. We examined the localization of the A-CAM molecule in heart by immunofluorescent microscopy. In contrast to normal cardiac samples, fluorescence was weak in intensity and unclearly demarcated in the Bio 14.6 hamsters. We measured the content of A-CAM in the heart. In Bio 14.6 hamsters, the content of A-CAM was 60 +/- 11% of that measured in normal adult hamsters. A-CAM was reduced to a lesser extent (81 +/- 12%) in the newborn hamsters. In Bio 14.6 hamster, structural disturbance of the intercalated disks was found on histological examination of the heart. Biochemically, A-CAM, which plays a role in intercellular adhesion in intercalated disk areas, decreased significantly. These results suggest that cardiomyopathy may be accompanied by structural disruption of cell-cell adhesion in intercalated disk regions, which may lead to the pathological feature of disarranged cardiomyocytes.