Potential role of human cytomegalovirus and p53 interaction in coronary restenosis.
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.
Speir
E
E
Cardiology Branch, National Institutes of Health, Bethesda, MD 20892.
Modali
R
R
Huang
E S
ES
Leon
M B
MB
Shawl
F
F
Finkel
T
T
Epstein
S E
SE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000800:Angioplasty, Balloon; D000956:Antigens, Viral / Q000378:metabolism*; D017225:Atherectomy, Coronary; D001483:Base Sequence; D002478:Cells, Cultured; D003327:Coronary Disease / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D003587:Cytomegalovirus / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D012008:Recurrence; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D016159:Tumor Suppressor Protein p53; C044582:immediate-early proteins, cytomegalovirus