title: Effects of human cytomegalovirus immediate-early proteins on p53-mediated apoptosis in coronary artery smooth muscle cells.
abstract: BACKGROUND
  Restenotic and atherosclerotic lesions often contain smooth muscle cells (SMCs), which display high rates of proliferation and apoptosis. Human cytomegalovirus (HCMV) may increase the incidence of restenosis and predispose 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 transcriptional activity. Given the role of p53 in mediating apoptosis, we studied the ability of IE2-84 to inhibit p53-dependent apoptosis in human coronary artery SMCs.
  
  
  RESULTS
  Apoptosis of SMCs was induced either by use of an adenovirus vector encoding human wild-type p53 protein or by treatment with doxorubicin. HCMV IE1-72 and IE2-84, the major IE proteins of HCMV, were overexpressed separately with adenovirus vectors encoding each protein, and the effects on p53-induced apoptosis were examined by both nick end-labeling (TUNEL) assay and flow cytometry. Expression of IE2-84, but not IE1-72, protected SMCs from p53-mediated apoptosis.
  
  
  CONCLUSIONS
  These data indicate that an HCMV IE protein antagonizes p53-mediated apoptosis, suggesting a pathway by which HCMV infection predisposes to SMC accumulation and thereby contributes to restenosis and atherosclerosis.
authors: Cardiology and the Pathology Branch, National Heart, Lung, and Blood Institute, and the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: K
authors: K
authors: Tanaka
authors: J P
authors: JP
authors: Zou
authors: K
authors: K
authors: Takeda
authors: V J
authors: VJ
authors: Ferrans
authors: G R
authors: GR
authors: Sandford
authors: T M
authors: TM
authors: Johnson
authors: T
authors: T
authors: Finkel
authors: S E
authors: SE
authors: Epstein
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D003587:Cytomegalovirus / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D015534:Trans-Activators; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins
chemical_list: C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus; D004317:Doxorubicin