Expression of cell division cycle 2 kinase transcription in chronically rejected cardiac allografts of nonhuman primates.

Accurate diagnosis and prevention of graft arteriosclerosis, known as chronic rejection, is critical to the success of cardiac transplantation, but often is difficult to attain. Expression of cell division cycle (cdc) 2 kinase, which plays a critical role in cell transition through the G2/M phase, is critical to the proliferation of vascular smooth muscle cells. To evaluate the usefulness of cdc2 kinase expression for pathophysiological analysis of chronic rejection, heterotopic cardiac transplantation was performed in Japanese monkeys (n = 7). Standard reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ RT-PCR were performed to evaluate the expression. In the coronary arteries of chronically rejected allografts, enhanced cdc2 kinase expression was observed in thickened intima and media, while none was expressed in native hearts. The cdc2 kinase was also expressed before the intimal thickening occurred. These results indicate that enhanced expression of cdc2 kinase is a sensitive indicator for chronic cardiac rejection; targeting cdc2 kinase may be a viable gene therapy for prevention of this vasculopathy.