Disorganization of intercalated discs in dilated cardiomyopathy

Yukinobu Ito,Daichi Maeda,Hirotake Masuda,Michinobu Umakoshi,Yukitsugu Kudo-Asabe,Hiroshi Nanjo,Akiteru Goto,Makoto Yoshida

doi:10.1038/s41598-021-90502-1

Yukinobu Ito, Daichi Maeda + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-90502-1

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Abstract

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in the intercalated discs (ICDs) between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 22 autopsy cases, including five DCM cases, nine CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized ICDs, clearly illustrated by N-cadherin immunostaining in the DCM group. “Reduction of N-cadherin immunostaining intensity” and “ICD scattering” was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM.

Highlights

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility
Our results reveal that intercalated discs (ICDs) disorganization is a characteristic of DCM and demonstrate that N-cadherin immunohistochemistry is useful for identifying this feature
Because N-cadherin is generally localized in ICDs, it stains as a single well-ordered band between cardiomyocytes

Summary

Introduction

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. We examined the morphological differences in the intercalated discs (ICDs) between three groups of patients, a DCM group, a chronic heart failure group, and a control group. The characteristic features of DCM include irregular cardiomyocyte hypertrophy, cardiomyocyte elongation, nuclear pleomorphism, diffuse interstitial fibrosis, and myofibrillar loss[16]. Some of these findings are occasionally encountered in dilated hearts resulting from cardiac diseases other than DCM. The ability of myocardial cells to adapt to physiological changes may involve the formation of appropriate junctions by which cells adhere to and communicate

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