title: Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts.
abstract: This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.
authors: Surgical Professorial Unit, St Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010, Sydney, Australia.
authors: A Y
authors: AY
authors: Wang
authors: Y V
authors: YV
authors: Bobryshev
authors: S M
authors: SM
authors: Cherian
authors: H
authors: H
authors: Liang
authors: D
authors: D
authors: Tran
authors: S J
authors: SJ
authors: Inder
authors: R S
authors: RS
authors: Lord
authors: K W
authors: KW
authors: Ashwell
authors: A E
authors: AE
authors: Farnsworth
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D016923:Cell Death / Q000235:genetics*; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006083:Graft Occlusion, Vascular / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012086:Reoperation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014680:Veins / Q000473:pathology / Q000637:transplantation*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases