EXPRESSION OF PROLIFERATING CELL MARKERS IN NORMAL AND DISEASED HUMANHEARTS

Proliferating cell nuclear antigen (PCNA) myocyte expression and histo pathologic features related to its occurrence were investigated in nor mal and diseased hearts of adult humans using both immunohistochemical and Western blotting techniques. Ki67 Western blotting was also perfo rmed in the same samples used for PCNA blotting. Two hundred seventy-o ne endomyocardial biopsies, and 15 adult, 1 embryonic and 2 fetal hear ts were studied. The biopsies were from normal donor hearts (n = 71), patients with cardiomyopathy and myocarditis (n = 64), and patients wi th transplantation with (n = 106) and without (n = 30) acute rejection of any grade. The 15 hearts were from 1 heart donor, and from patient s with cardiomyopathy (n = 5), valvular heart disease (n = 2), ischemi c heart disease (n = 4), amyloidosis (n = 1) and transplantation with acute rejection (n = 2). The PCNA labeling index was plotted against m yocyte hypertrophy, inflammatory infiltrates and binucleation index. T he PCNA labeling index ranged from 2 to 9% in embryonic and fetal hear ts. PCNA was expressed by 1 to 2% of myocyte nuclei in 12% of normal h eart biopsies, 1 to 5% of myocyte nuclei in 28% of cardiomyopathy and myocarditis biopsies, and by up to 8% of myocyte nuclei in 53% of biop sies of patients with transplantation, independently of the presence a nd degree of acute rejection. In the latter biopsies and in myocarditi s, some inflammatory cells also showed PCNA expression. PCNA positive myocytes were both mono- and binucleated, and there was no correlation between binucleation and PCNA labeling indexes. Ki67 and PCNA blottin g confirmed immunohistochemical results. The results show that few myo cytes express PCNA in normal hearts. This expression is only detectabl e by immunohistochemical stains. The percentage of PCNA expressing myo cytes increases in diseased hearts of any origin, so that it becomes d etectable by both immunohistochemical and Western blotting techniques. Data from planted heart biopsies confirm that as in my ditis, immunol ogic-inflammatory stimuli are likely powerful triggers of PCNA express ion. Therefore, cardiac myocytes of adult humans can express prolifera ting cell markers, and this expression increase in hearts with hypertr ophy or inflammatory reaction.