THE WAF1-MEDIATED P53 GROWTH-SUPPRESSOR PATHWAY IS INTACT IN THE CORONARY-ARTERIES OF HEART-TRANSPLANT RECIPIENTS

has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids hav e been observed in the coronary arteries of allografted hearts, sugges ting a possible role for the interaction of CMV with p53 in the develo pment of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 1 9 transplanted hearts were immunostained for the p53 gene product usin g Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the a nti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arte ries were also available from six of the 19 hearts, and these fresh-fr ozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and we ak staining for p53 was observed in smooth muscle and endothelial cell s in two of 19 vessels, whereas the remaining 17 did not stain. CMV nu cleic acids were previously shown in six of 13 of these hearts by in s itu hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels d id stain intensely for WAF1. These results suggest three possibilities : (1) CMV-p53 interactions are not important in the development of acc elerated graft arteriosclerosis; or (2) there is an interaction, but i t is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-EG. The express ion of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels. (C) 1996 by W.B. Saunders Company