title: The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients.
abstract: It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.
authors.affiliation: Department of Pathology of the Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: I O
authors.initials: IO
authors.lastname: Baas
authors.forename: J A
authors.initials: JA
authors.lastname: Offerhaus
authors.forename: W S
authors.initials: WS
authors.lastname: El-Deiry
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
authors.forename: G M
authors.initials: GM
authors.lastname: Hutchins
authors.forename: E K
authors.initials: EK
authors.lastname: Kasper
authors.forename: K L
authors.initials: KL
authors.lastname: Baughman
authors.forename: W A
authors.initials: WA
authors.lastname: Baumgartner
authors.forename: C J
authors.initials: CJ
authors.lastname: Chiou
authors.forename: G S
authors.initials: GS
authors.lastname: Hayward
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
mesh_terms: D003324:Coronary Artery Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications*; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early / Q000235:genetics; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53