Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, Bleese N
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, Nauheim, FRG.
Circulation. 1991 Feb;83(2):504-14. doi: 10.1161/01.cir.83.2.504.
This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.
本研究旨在确定慢性心力衰竭的形态学关联因素。对8例因终末期扩张型心肌病接受移植手术患者的心肌组织进行了电子显微镜检查和免疫细胞化学分析，使用针对细胞骨架成分的单克隆抗体：结蛋白、微管蛋白、纽蛋白和波形蛋白。组织显示有心肌肥大、心肌细胞萎缩以及纤维化增加。超微结构改变包括细胞核增大且形状各异、大量非常小的线粒体、T小管增生以及脂滴和糖原积聚。最明显的超微结构改变是肌丝减少，从稀疏到充满未明确细胞质的细胞中肌节完全缺失。免疫细胞化学显示结蛋白定位于Z线。在患病心肌中，结蛋白量增加，但排列紊乱。微管蛋白在整个心肌细胞中形成精细网络，在心肌病心脏中显著增加。纽蛋白是一种与细胞骨架密切相关的蛋白质，不仅出现在肌膜和闰盘，也出现在心肌细胞内。约三分之一的细胞超微结构改变和细胞骨架改变严重。约三分之一的细胞显示中度严重改变，其余细胞正常。波形蛋白存在于间质细胞中，并随纤维化增加而增多。我们得出结论，纤维化增加、肥大心肌细胞变性以及细胞骨架改变是慢性心力衰竭心肌功能降低的形态学关联因素。
