Effects of human cytomegalovirus immediate-early proteins on p53-mediated apoptosis in coronary artery smooth muscle cells

Background-Restenotic and atherosclerotic lesions often contain smooth musc le cells (SMCs), which display high rates of proliferation and apoptosis. H uman cytomegalovirus (HCMV) may increase the incidence of restenosis and pr edispose to atherosclerosis. Although the mechanisms contributing to these processes are unclear, studies demonstrate that one of the immediate-early (IE) gene products of HCMV, IE2-84, binds to and inhibits p53 transcription al activity. Given the role of p53 in mediating apoptosis, we studied the a bility of IE2-84 to inhibit p53-dependent apoptosis in human coronary arter y SMCs. Methods and Results-Apoptosis of SMCs was induced either by use of an adeno virus vector encoding human wild-type p53 protein or by treatment with doxo rubicin. HCMV IE1-72 and IE2-84, the major IE proteins of HCMV, were overex pressed separately with adenovirus vectors encoding each protein, and the e ffects on p53-induced apoptosis were examined by both nick end-labeling (TU NEL) assay and flow cytometry. Expression of IE2-84, but not IE1-72, protec ted SMCs fi om p53-mediated apoptosis, Conclusions-These data indicate that an HCMV IE protein antagonizes p53-med iated apoptosis, suggesting a pathway by which HCMV infection predisposes t o SMC accumulation and thereby contributes to restenosis and atherosclerosi s.