Kostin S, Hein S, Arnon E, Scholz D, Schaper J
Max Planck Institute, Kerckhoff-Clinic, Dept. of Cardiac Surgery, Bad Nauheim, Germany.
Heart Fail Rev. 2000 Oct;5(3):271-80. doi: 10.1023/A:1009813621103.
In addition to functional alterations, heart failure has a structural basis as well. This concerns all components of the cardiac myocytes as well as the extracellular space. Proteins of the cardiomyocyte can be subdivided in 5 different categories: 1) Contractile proteins including myosin, actin, tropomyosin and the troponins. 2) Sarcomeric skeleton: titin, myosin binding protein C, alpha-actinin, myomesin, and M-protein. 3) True 'cytoskeletal' proteins: tubulin, desmin and actin. 4) Membrane-associated proteins: dystrophin, spectrin, talin, vinculin, ankyrin and others. 5) Proteins of the intercalated disc: desmosomes consisting of desmoplakin, desmocollin, desmoglein and desmin; adherens junctions with N-cadherin, the catenins and vinculin, and gap junctions with connexin. Failing myocardium obtained from patients undergoing cardiac transplantation exhibits ultrastuctural degeneration and an altered nucleus/cytoplasm relationship. The contractile proteins and those of the sarcomeric skeleton, especially titin, are downregulated, the cytoskeletal proteins desmin and tubulin and membrane-associated proteins such as vinculin and dystrophin are upregulated and those of the intercalated disc are irregularly arranged. Elevation of cytoskeletal proteins correlates well with diastolic and contractile dysfunction in these patients. The enlarged interstitial space contains fibrosis, i.e. accumulations of fibroblasts and extracellular matrix components, in addition to macrophages and microvascular elements. Loss of the contractile machinery and related proteins such as titin and alpha-actinin may be the first and decisive event initiating an adaptive increase in cytoskeleton and membrane associated components. Fibrosis may be stimulated by subcellular degeneration. The hypothesis is put forward that all proteins of the different myocardial compartments contribute to the deterioration of cardiac function in heart failure.
除了功能改变外，心力衰竭还有结构基础。这涉及心肌细胞的所有成分以及细胞外间隙。心肌细胞的蛋白质可分为5种不同类别：1）收缩蛋白，包括肌球蛋白、肌动蛋白、原肌球蛋白和肌钙蛋白。2）肌节骨架：肌联蛋白、肌球蛋白结合蛋白C、α-辅肌动蛋白、肌间线蛋白和M蛋白。3）真正的“细胞骨架”蛋白：微管蛋白、结蛋白和肌动蛋白。4）膜相关蛋白：肌营养不良蛋白、血影蛋白、踝蛋白、纽蛋白、锚蛋白等。5）闰盘蛋白：由桥粒斑蛋白、桥粒芯蛋白、桥粒糖蛋白和结蛋白组成的桥粒；与N-钙黏着蛋白、连环蛋白和纽蛋白相连的黏着连接，以及与连接蛋白相连的缝隙连接。从接受心脏移植的患者获取的衰竭心肌表现出超微结构退变以及核/质关系改变。收缩蛋白和肌节骨架蛋白，尤其是肌联蛋白，表达下调，细胞骨架蛋白结蛋白和微管蛋白以及膜相关蛋白如纽蛋白和肌营养不良蛋白表达上调，闰盘蛋白排列不规则。这些患者中细胞骨架蛋白升高与舒张和收缩功能障碍密切相关。扩大的间质空间除了含有巨噬细胞和微血管成分外，还存在纤维化，即成纤维细胞和细胞外基质成分的积聚。收缩机制以及相关蛋白如肌联蛋白和α-辅肌动蛋白的丧失可能是引发细胞骨架和膜相关成分适应性增加的首个决定性事件。纤维化可能受到亚细胞退变的刺激。有人提出假说，即不同心肌成分的所有蛋白质都促成了心力衰竭时心脏功能的恶化。
