Dispersyn G D, Mesotten L, Meuris B, Maes A, Mortelmans L, Flameng W, Ramaekers F, Borgers M
Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Eur Heart J. 2002 Jun;23(11):849-57. doi: 10.1053/euhj.2001.2963.
Cardiomyocyte apoptosis is known to occur in infarct border zones, where cardiomyocyte dedifferentiation, as seen in hibernating myocardium, can also be observed. The aim of the study is to determine whether dedifferentiated cardiomyocytes represent a population of cells stably surviving or undergoing apoptosis.
Microinfarctions were induced in sheep (n=8) by intracoronary injection of polymer macrobeads. The sheep were killed when cardiac function was gradually decreased (ejection fraction 37+/-6%, mean+/-SEM), but not earlier than 6 weeks after embolization. Transmural biopsies were taken from embolized and remote areas, based on flow measurements with positron emission tomography. Cells were classified as dedifferentiated when sarcomere content was depleted by >10% and glycogen content increased. Apoptosis was detected using the Tdt-mediated nick-end labelling (TUNEL) method and activated caspase-3 immunolabelling. Dedifferentiated cardiomyocytes were identified by morphology and by immunohistochemical evaluation of dedifferentiation related expression patterns of desmin, titin, cardiotin and alpha-smooth muscle actin. Cardiomyocyte apoptosis was detected in both the infarction border zones and remote areas. Dedifferentiated cardiomyocytes accounted for up to 30% of the cells in embolized areas and were almost exclusively non-apoptotic.
In embolization induced microinfarcted tissue, dedifferentiated cardiomyocytes are preferentially spared to undergo apoptosis. It is hypothesized that dedifferentiated cardiomyocytes and apoptotic cardiomyocytes represent two different cell populations. The dedifferentiated cells can be considered as stable surviving cells.
已知心肌细胞凋亡发生在梗死边缘区，在该区域也可观察到心肌细胞去分化现象，如在冬眠心肌中所见。本研究的目的是确定去分化的心肌细胞是代表稳定存活的细胞群体还是正在经历凋亡的细胞群体。
通过冠状动脉内注射聚合物微珠在绵羊（n = 8）中诱导微梗死。当心脏功能逐渐下降（射血分数37±6%，平均值±标准误）时处死绵羊，但不早于栓塞后6周。基于正电子发射断层扫描的血流测量，从栓塞区域和远处区域获取透壁活检组织。当肌节含量减少>10%且糖原含量增加时，细胞被分类为去分化细胞。使用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法和活化的半胱天冬酶-3免疫标记检测凋亡。通过形态学以及对结蛋白、肌联蛋白、心肌肌钙蛋白和α-平滑肌肌动蛋白的去分化相关表达模式进行免疫组织化学评估来鉴定去分化的心肌细胞。在梗死边缘区和远处区域均检测到心肌细胞凋亡。去分化的心肌细胞占栓塞区域细胞的比例高达30%，且几乎完全没有凋亡。
在栓塞诱导的微梗死组织中，去分化的心肌细胞优先免于凋亡。据推测，去分化的心肌细胞和凋亡的心肌细胞代表两个不同的细胞群体。去分化的细胞可被视为稳定存活的细胞。
