Abstract P036: Regional Characterization of Myocardial Renewal in Humans

Abstract

We and other groups have reported cardiomyocyte renewal in adult human hearts. However, there is no consensus about magnitude and regional heterogeneity in myocardial turnover. Important requirements to quantify cellular turnover are the accurate identification of cardiomyocytes and ploidy level. We present a regional analysis of turnover in the adult myocardium, using the integration of atmospheric radiocarbon (14C) into genomic myocardial DNA. Cardiomyocyte nuclei were labeled with pericentriolar protein 1 (PCM-1) and isolated by flow cytometry. In order to improve estimates on cardiomyocyte turnover, nuclei were isolated according to their DNA content. A substantial fraction of cardiomyocyte nuclei in the right and left ventricle were polyploid: 28.9%±10.6% diploid, 58.9%±8.5% tetraploid and 12.1%±7.4% octaploid in the left ventricle and 47.9%±10.6% diploid, 46.6%±8.3% tetraploid and 5.6%±3.2% octaploid in the right ventricle. Cardiomyocyte turnover was analyzed according to their ploidy distribution in the left and right ventricle. Data from this ongoing study indicates a limited regenerative potential in both ventricles. A comprehensive mathematical analysis of regional turnover distribution will be presented. Non-cardiomyocytes were in average 18.0±2.3 years younger than the respective subjects, indicating a substantial turnover in the whole myocardium. The human heart has the capability to regenerate cardiomyocytes. However, the magnitude of this process does not allow for the renewal of the whole myocardium under homeostatic condition in a lifetime. Understanding the underlying mechanisms of cardiac renewal will open up new avenues to treat cardiac injuries.