Zuppinger C, Eppenberger-Eberhardt M, Eppenberger H M
Dept. of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology ETH, CH-8093, Zurich, Switzerland.
Heart Fail Rev. 2000 Oct;5(3):251-7. doi: 10.1023/A:1009809520194.
N-Cadherin belongs to a superfamily of calcium-dependent transmembrane adhesion proteins. It mediates adhesion in the intercalated discs at the termini of cardiomyocytes thereby serving as anchor for myofibrils at cell-cell contacts. A large body of data on the molecular structure and function of N-cadherin exists, however, little is known concerning spatial and temporal interactions between the different junctional structures during formation of the intercalated disc and its maturation in postnatal development. The progression of compensated left ventricular hypertrophy to congestive left heart failure is accompanied by intercalated disc remodeling and has been demonstrated in animal models and in patients. The long-term culture of adult rat cardiomyocytes allows to investigate the development of de novo intercalated disc-like structures. In order to analyze the dynamics of the cytoskeletal redifferentiation in living cells, we used the expression of chimeric proteins tagged with the green fluorescent protein reporter. This technique is becoming a routine method in basic research and complements video time-lapse and confocal microscopy. Cultured cardiomyocytes have been used for a variety of studies in cell biology and pharmacology. Their ability to form an electrically coupled beating tissue-like network in culture possibly allows reimplantation of such cells into injured myocardium, where they eventually will form new contacts with the healthy muscle tissue. Several groups have already shown that cardiomyocytes can be grafted successfully into sites of myocardial infarcts or cryoinjuries. Autologous adult cardiomyocyte implantation, might indeed contribute to cardiac repair after infarction, thanks to advances in tissue engineering.
N-钙黏着蛋白属于钙依赖性跨膜黏附蛋白超家族。它介导心肌细胞末端闰盘中的黏附,从而在细胞间接触处作为肌原纤维的锚定物。关于N-钙黏着蛋白的分子结构和功能已有大量数据,然而,关于出生后发育过程中闰盘形成及其成熟过程中不同连接结构之间的时空相互作用却知之甚少。代偿性左心室肥厚向充血性左心衰竭的进展伴随着闰盘重塑,这已在动物模型和患者中得到证实。成年大鼠心肌细胞的长期培养有助于研究从头形成的闰盘样结构的发育。为了分析活细胞中细胞骨架再分化的动态过程,我们使用了带有绿色荧光蛋白报告基因的嵌合蛋白表达。这项技术正在成为基础研究中的常规方法,并补充了视频延时和共聚焦显微镜技术。培养的心肌细胞已被用于细胞生物学和药理学的各种研究。它们在培养中形成电耦合搏动组织样网络的能力可能允许将此类细胞重新植入受损心肌,在那里它们最终将与健康肌肉组织形成新的接触。几个研究小组已经表明,心肌细胞可以成功移植到心肌梗死或冷冻损伤部位。由于组织工程的进展,自体成年心肌细胞植入确实可能有助于梗死心脏的修复。