Potential Role of Human Cytomegalovirus and p53 Interaction in Coronary Restenosis

Abstract

A subset of patients who have undergone coronary angioplasty develop restenosis, a vessel renarrowing characterized by excessive proliferation of smooth muscle cells (SMCs). Of 60 human restenosis lesions examined, 23 (38 percent) were found to have accumulated high amounts of the tumor suppressor protein p53, and this correlated with the presence of human cytomegalovirus (HCMV) in the lesions. SMCs grown from the lesions expressed HCMV protein IE84 and high amounts of p53. HCMV infection of cultured SMCs enhanced p53 accumulation, which correlated temporally with IE84 expression. IE84 also bound to p53 and abolished its ability to transcriptionally activate a reporter gene. Thus, HCMV, and IE84-mediated inhibition of p53 function, may contribute to the development of restenosis.

Apoptosis in the vasculature: mechanisms and functional importance

“…High cellularity is a key ®nding in late human restenosis and the ®ndings of Bauriedel et al (1998) are more consistent with the paradigm that lower rates of apoptosis result in hyperplasia. This also ®ts well with the ®nding of decreased p53 activity (and potentially p53-mediated apoptosis) in restenotic material from human coronary lesions (Speir et al, 1994).…”

The Role of Viruses in Cardiac Allograft Vasculopathy

“…Similar results were obtained in the HOPE (Heart Outcomes and Prevention Evaluation) study showing that out of the four pathogens tested (Cpn, Hpyl, hepatitis A, CMV) only CMV serostatus was predictive of cardiovascular events (29). The association with CMV seems to be more pronounced in connection with rapidly progressing atherosclerotic processes such as coronary restenosis after angioplasty or vascular surgery (18), and this observation might be of relevance to CAV in view of its rapid time course.…”

“…Additionally, an immediate early gene product of HCMV, IE2-84, has been shown to bind with and inhibit the tumor suppressor gene, P53 (18,19). This may explain how abortive CMV infections lead to increased expression of growth factors and growth factor receptors, and to smooth muscle cell proliferation and migration, and inhibition of apoptosis (20).…”

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…Later, it was discovered that viral oncoproteins from other DNA tumour viruses have the properties to bind p53. Thus the adenovirus E1B (Sarnow et al, 1982) and human papillomavirus HPV E6 protein (Sche ner et al, 1990), Epstein ± Barr virus nuclear antigen (Szekely et al, 1993), hepatitis B virus X protein and human cytomegalovirus IE84 protein (Speir et al, 1994), form complexes with the p53 protein.…”