Hemodynamic Support by Left Ventricular Assist Devices Reduces Cardiomyocyte DNA Content in the Failing Human Heart
- 2 March 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 121 (8), 989-996
- https://doi.org/10.1161/circulationaha.108.808071
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.Keywords
This publication has 20 references indexed in Scilit:
- Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injuryNature Medicine, 2007
- Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changesCardiovascular Research, 2005
- Cardiac Stem Cells and Mechanisms of Myocardial RegenerationPhysiological Reviews, 2005
- Endomitosis and polyploidization of myocardial cells in the periphery of human acute myocardial infarctionCardiovascular Research, 2005
- Adult Cardiac Stem Cells Are Multipotent and Support Myocardial RegenerationCell, 2003
- Evidence That Human Cardiac Myocytes Divide after Myocardial InfarctionThe New England Journal of Medicine, 2001
- Bone marrow cells regenerate infarcted myocardiumNature, 2001
- Cardiac myocyte nuclear size and ploidy status decrease after mechanical supportCardiovascular Pathology, 2001
- Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical supportThe Journal of Heart and Lung Transplantation, 2000
- Use of a mechanical dissociation device to improve standardization of flow cytometric cytokeratin DNA measurements of colon carcinomasCytometry, 1999