Sharov Victor G, Kostin Sawa, Todor Anastassia, Schaper Jutta, Sabbah Hani N
Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan 48202, USA.
Heart Fail Rev. 2005 Dec;10(4):297-303. doi: 10.1007/s10741-005-7544-2.
In the setting of chronic heart failure (HF), progressive left ventricular (LV) dysfunction and chamber remodeling may be due, in part, to altered expression and disorganization of cytoskeletal, linkage and extracellular proteins. This brief review describes changes in expression of cytoskeletal, linkage and extracellular protein using LV tissue obtained from dogs with progressive HF produced by multiple sequential intracoronary microembolizations. LV tissue samples from 6 untreated HF dogs (LV ejection fraction 20% to 25%) and 3 normal dogs were used. Sections from freshly frozen tissue were prepared, immunostained for specific proteins and studies by confocal microscopy. In failing hearts, confocal microscopy showed disorganization of key cytoskeletal proteins that, when combined with the loss of myofilaments and sarcomeric skeleton, suggest substantial cardiomyocyte remodeling. Cardiomyocytes in areas bordering old infarcts invariably exhibited disorganization of alpha-actinin. The cytoskeleton protein desmin showed increased expression in areas of extensive fibrosis. Staining for pancadherin showed interruptions of intercalated disks in areas of intensive interstitial fibrosis. Observation of increased fibronectin and increased interstitial cellularity based on vimentin labeling is suggestive of ongoing fibrosis. Based on these findings, we conclude that the structural changes observed in failing LV myocardium of dogs with intracoronary microembolizations-induced HF are extensive and typical of those seen and previously described in LV myocardium of explanted failed human hearts. The observed structural changes in this experimental model of HF also support the notion that these cytoskeletal, linkage and extracellular disorganization of structural proteins may be important maladaptations that contribute, albeit in part, to the progression of LV dysfunction and remodeling characteristic of the HF state.
在慢性心力衰竭（HF）的情况下，进行性左心室（LV）功能障碍和心室重塑可能部分归因于细胞骨架、连接蛋白和细胞外蛋白的表达改变及结构紊乱。本简要综述描述了使用从经多次连续冠状动脉内微栓塞产生进行性HF的犬类获取的LV组织，观察细胞骨架、连接蛋白和细胞外蛋白表达的变化。使用了6只未经治疗的HF犬（LV射血分数20%至25%）和3只正常犬的LV组织样本。制备新鲜冷冻组织的切片，对特定蛋白质进行免疫染色，并通过共聚焦显微镜进行研究。在衰竭心脏中，共聚焦显微镜显示关键细胞骨架蛋白的结构紊乱，这与肌丝和肌节骨架的丧失相结合，提示心肌细胞发生了显著重塑。与陈旧性梗死灶相邻区域的心肌细胞总是表现出α-辅肌动蛋白的结构紊乱。细胞骨架蛋白结蛋白在广泛纤维化区域的表达增加。全钙黏蛋白染色显示在密集的间质纤维化区域闰盘中断。基于波形蛋白标记观察到纤连蛋白增加和间质细胞增多提示正在发生纤维化。基于这些发现，我们得出结论，在冠状动脉内微栓塞诱导的HF犬的衰竭LV心肌中观察到的结构变化广泛，并且与在移植的衰竭人心脏的LV心肌中所见及先前描述的典型变化一致。在该HF实验模型中观察到的结构变化也支持这样的观点，即这些结构蛋白的细胞骨架、连接和细胞外结构紊乱可能是重要的适应不良，尽管只是部分地导致了HF状态特有的LV功能障碍和重塑的进展。
