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左心室辅助装置的血液动力学支持可减少衰竭人心肌细胞的 DNA 含量。

Hemodynamic support by left ventricular assist devices reduces cardiomyocyte DNA content in the failing human heart.

机构信息

Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr 55, 45147 Essen, Germany.

出版信息

Circulation. 2010 Mar 2;121(8):989-96. doi: 10.1161/CIRCULATIONAHA.108.808071. Epub 2010 Feb 16.

DOI:10.1161/CIRCULATIONAHA.108.808071
PMID:20159834
Abstract

BACKGROUND

Whether adult cardiomyocytes have the capacity to regenerate in response to injury and, if so, to what extent are still issues of intense debate. In human heart failure, cardiomyocytes harbor a polyploid genome. A unique opportunity to study the mechanism of polyploidization is provided through the setting of hemodynamic support by left ventricular assist devices. Hence, the cardiomyocyte DNA content, nuclear morphology, and number of nuclei per cell were assessed before and after left ventricular assist device support.

METHODS AND RESULTS

In 23 paired myocardial samples, cardiomyocyte ploidy was investigated by DNA image cytometry, flow cytometry, and in situ hybridization. Nuclear cross-sectional area and perimeters were measured morphometrically, and the binucleated cardiomyocytes were counted. The median of the cardiomyocyte DNA content and the number of polyploid cardiomyocytes both declined significantly from 6.79 c to 4.7 c and 40.2% to 23%, whereas a significant increase in diploid cardiomyocytes from 33.4% to 50.3% and in binucleated cardiomyocytes from 4.5% to 10% after unloading was observed.

CONCLUSIONS

The decrease in polyploidy and increase in diploidy after left ventricular assist device suggest a numeric increase in diploid cardiomyocytes (eg, through cell cycle progression with completion of mitosis or by increased stem cells). The cardiac regeneration that follows may serve as a morphological correlate of the recovery observed in some patients after unloading.

摘要

背景

成年心肌细胞是否具有响应损伤而再生的能力,如果有,其程度如何,这仍然是一个激烈争论的问题。在人类心力衰竭中,心肌细胞具有多倍体基因组。通过左心室辅助设备提供的血液动力学支持,可以为研究多倍体化的机制提供独特的机会。因此,在左心室辅助设备支持前后评估了心肌细胞的 DNA 含量、核形态和每个细胞的核数。

方法和结果

在 23 对配对的心肌样本中,通过 DNA 图像细胞计量术、流式细胞术和原位杂交研究了心肌细胞的倍性。通过形态计量法测量核横截面积和周长,并计数双核心肌细胞。心肌细胞 DNA 含量和多倍体心肌细胞数量的中位数均从 6.79c 显著下降至 4.7c 和 40.2%至 23%,而卸载后二倍体心肌细胞从 33.4%显著增加至 50.3%,双核心肌细胞从 4.5%增加至 10%。

结论

左心室辅助设备后多倍体减少和二倍体增加表明二倍体心肌细胞数量增加(例如,通过完成有丝分裂的细胞周期进展或通过增加干细胞)。随后的心脏再生可能是一些患者在卸载后观察到的恢复的形态学相关。

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