PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA), DNA-SYNTHESIS AND MITOSIS IN MYOCYTES FOLLOWING CARDIAC TRANSPLANTATION IN MAN

Cardiac transplantation is characterized by rejection, myocyte loss, i nterstitial and replacement fibrosis, and loading abnormalities. These modifications contribute to enhance mural and muscle cell stress, act ivating reactive growth processes in myocytes and interstitial cells: However, it is unknown whether cell cycle related gene product, such a s PCNA, and DNA synthesis are stimulated under these conditions. There fore, 62 endomyocardial biopsies obtained from 17 patients who underwe nt cardiac transplantation were examined for the immunocytochemical de tection of PCNA protein in myocyte and non-myocyte nuclei. In addition , tissue samples were labeled in vitro with bromodeoxyuridine (BrdU) t o document ongoing DNA synthesis. The presence of mitotic images in my ocytes and non myocytes were also examined. Biopsies were collected fr om 1-768 days after surgery. Histologic examination of tissue sections documented that PCNA labeling involved nearly 30% of myocyte nuclei i n all patients. Similar percentages of PCNA labeling were detected in interstitial cells, lymphocytes and mononuclear infiltrates. DNA synth esis in myocytes and connective tissue cells was observed in nine and 14 subjects; respectively. BrdU positive lymphocytes and mononuclear i nfiltrates in 13 cases. Three mitotic figures in myocyte nuclei were i dentified. PCNA, BrdU labeling and mitosis were not detected in eight myocardial samples obtained from control hearts. These results suggest that the evolution of the transplanted heart involves the expression of a gene which is implicated in DNA replication. The presence of ongo ing DNA synthesis and mitosis support the notion that proliferation of myocytes and non muscle cells may be a component of ventricular remod eling after cardiac transplantation. (C) 1997 Academic Press Limited.