Endomitosis and polyploidization of myocardial cells in the periphery of human acute myocardial infarction
Endomitosis and polyploidization of myocardial cells in the periphery of human acute myocardial infarction
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DOI：
10.1016/j.cardiores.2005.02.017
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发表时间：
2005-07-01
影响因子：
10.8
通讯作者：
Laguens, R
中科院分区：
文献类型：
--
作者：
Meckert, PC;Rivello, HG;Laguens, R
目的：尽管有丝分裂后的心肌细胞中存在重新启动DNA合成的遗传程序，并且据报道，在人类急性心肌梗死（AMI）中，有相当比例的心肌细胞进入有丝分裂，但规律是失去的组织被胶原疤痕所取代。本研究的目的是寻找这种不一致的基础，以便设计未来的策略来诱导肌细胞分裂成子细胞，用收缩细胞代替失去的组织。方法：采用免疫酶法、光共聚焦显微镜、激光共聚焦显微镜和密度测定法，对15例梗死1 ~ 21 D的人心脏梗死区周围心肌细胞的细胞周期蛋白Ki67抗原、细胞周期蛋白D、A、B1的表达、有丝分裂体的存在和倍体状态进行研究。结果：7 ~ 13 D梗死后，11.61 +/- 6.94%的心肌细胞呈现Ki67+核，较低比例呈现细胞周期蛋白D、a、b。早期和晚期，Ki67+肌细胞比例均显著降低。虽然在共聚焦显微镜和荧光标记下，一些Ki67+肌细胞似乎处于有丝分裂的不同阶段，用诺玛斯基光学和苏木精反染，浓缩的染色体，虽然排列在中期和后期板或在姐妹染色单体中分裂，但总是位于保存的核膜内，表明有丝分裂的存在。常规有丝分裂异常。在14天和21天的梗死中，梗死附近肌细胞的倍性明显高于远处区域。结论：这些观察结果表明，在人类梗死中，心肌细胞进入细胞周期是短暂的，周期细胞的最终命运是内膜分裂，导致多倍体，而不是有丝分裂，导致核分裂。这两种观察结果可能解释了心肌细胞再生能力与人类AMI缺乏有效修复过程之间的不一致。(c) 2005年欧洲心脏病学会。Elsevier B.V.版权所有。
Objective: Although the genetic program for reinitiating DNA synthesis exists in post-mitotic cardiomyocytes, and it was reported that in human acute myocardial infarction (AMI) a significant proportion of myocytes enter mitosis, the rule is that the lost tissue is replaced by a collagen scar. The purpose of this study was to search for the basis of this discordance in order to devise future strategies to induce division of myocytes into daughter cells that may replace the lost tissue with contractile cells.Methods: In 15 human hearts with 1- to 21-day-old infarcts, the expression of the cell cycle proteins Ki67 antigen, cyclins D, A, and B1, the presence of mitotic bodies, and the ploidy status were investigated with immunoenzymatic methods, light and laser confocal microscopy, and densitometry in the myocytes surrounding the infarct area.Results: In 7- to 13-day-old infarcts, 11.61 +/- 6.94% of the myocytes presented Ki67+ nuclei, and a lower proportion presented cyclins D, A, and B. At earlier and later times, the proportion of Ki67+ myocytes was significantly lower. Although under confocal microscopy and fluorescent labels, some of the Ki67+ myocytes appeared to be in different stages of mitosis, with Nomarski optics and hematoxylin counterstaining, the condensed chromosomes, although arranged in metaphase and anaphase plates or split in sister chromatids, were always located within a preserved nuclear envelope, indicating the presence of endomitosis. Conventional mitosis was exceptionally observed. In the 14- and 21-day-old infarcts, the ploidy of the myocytes adjacent to the infarct was significantly higher than in distant zones.Conclusion: These observations indicate that in human infarcts, entrance of cardiomyocytes into the cell cycle is transient and that endomitosis, leading to polyploidy, rather than mitosis, leading to karyokinesis, is the final fate of cycling cells. Both observations may account for the discordance between the regenerative ability of myocytes and the lack of an efficient reparative process in human AMI. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.