Adaptations of cytoarchitecture in human dilated cardiomyopathy.

Marlene Pluess,Elisabeth Ehler,Cristobal G Dos Remedios,Gregor Daeubler

doi:10.1007/s12551-014-0146-2

Abstract

Hypertrophic cardiomyopathy is characterised by a histological phenotype of myocyte disarray, but heart tissue samples from patients with dilated cardiomyopathy (DCM) often look comparatively similar to those from healthy individuals apart from conspicuous regions of fibrosis and necrosis. We have previously investigated subcellular alterations in the cytoarchitecture of mouse models of dilated cardiomyopathy and found that both the organisation and composition of the intercalated disc, i.e. the specialised type of cell–cell contact in the heart, is altered. There is also is a change in the composition of the M-band of the sarcomere due to an expression shift towards the more extensible embryonic heart (EH)-myomesin isoform. Analysis of human samples from the Sydney Human Heart Tissue Bank have revealed similar structural findings and also provided evidence for a dramatic change in overall cardiomyocyte size control, which has also been seen in the mouse. Together these changes in cytoarchitecture probably contribute to the decreased functional output that is seen in DCM.

Highlights

Hypertrophic cardiomyopathy is characterised by a histological phenotype of myocyte disarray, but heart tissue samples from patients with dilated cardiomyopathy (DCM) often look comparatively similar to those from healthy individuals apart from conspicuous regions of fibrosis and necrosis
hypertrophic cardiomyopathy (HCM) is characterised by the re-expression of a set of marker genes that are usually not detectable in the postnatal heart, including those for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) or of the embryonic isoforms of, for example, contractile proteins such as myosin and actin (MacLellan and Schneider 2000; Copeland et al 2010)
DCM Dilated cardiomyopathy, IDCM idiopathic DCM, FDCM familial DCM, VDCM viral-caused DCM a Non-failing and DCM heart sample sections were stained for laminin and beta-catenin to delineate the cell borders and myomesin for cardiomyocyte identification

Summary

Introduction

Hypertrophic cardiomyopathy is characterised by a histological phenotype of myocyte disarray, but heart tissue samples from patients with dilated cardiomyopathy (DCM) often look comparatively similar to those from healthy individuals apart from conspicuous regions of fibrosis and necrosis. Most sarcomeric proteins, such as alpha-actinin (a component of the Z-disc), myomesin (a component of the M-band) and thin and thick filament proteins [cardiac actin, sarcomeric myosin or MyBP-C (muscle protein myosin binding protein C)] do not alter their expression levels or their localisation patterns in DCM (Ehler et al 2001). In DCM, a similar switch in expression to a more extensible, embryonic isoform of a protein has been reported for titin (Makarenko et al 2004), an elastic filament protein that spans all the way from the Z-disc to the M-band.

Results

Conclusion