Pluess Marlene, Daeubler Gregor, Dos Remedios Cristobal G, Ehler Elisabeth
Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
Bosch Institute, Department of Anatomy, University of Sydney, Sydney, 2006, Australia.
Biophys Rev. 2015 Mar;7(1):25-32. doi: 10.1007/s12551-014-0146-2. Epub 2014 Dec 11.
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.
肥厚型心肌病的组织学表型特征为心肌细胞排列紊乱，但扩张型心肌病（DCM）患者的心脏组织样本，除了有明显的纤维化和坏死区域外，通常看起来与健康个体的样本较为相似。我们之前研究了扩张型心肌病小鼠模型细胞结构的亚细胞改变，发现闰盘（即心脏中特殊类型的细胞间连接）的组织结构和组成均发生了改变。由于向更具伸展性的胚胎心脏（EH）-肌间蛋白异构体的表达转变，肌节M带的组成也发生了变化。对悉尼人类心脏组织库的人类样本分析揭示了类似的结构发现，同时也为心肌细胞整体大小控制的显著变化提供了证据，这种变化在小鼠中也有观察到。这些细胞结构的变化共同作用，可能导致了扩张型心肌病中所见的功能输出下降。
