PMID- 11420155 OWN - NLM STAT- MEDLINE DCOM- 20010830 LR - 20191025 IS - 0967-2109 (Print) IS - 0967-2109 (Linking) VI - 9 IP - 4 DP - 2001 Aug TI - Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts. PG - 319-28 AB - 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. FAU - Wang, A Y AU - Wang AY AD - Surgical Professorial Unit, St Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010, Sydney, Australia. FAU - Bobryshev, Y V AU - Bobryshev YV FAU - Cherian, S M AU - Cherian SM FAU - Liang, H AU - Liang H FAU - Tran, D AU - Tran D FAU - Inder, S J AU - Inder SJ FAU - Lord, R S AU - Lord RS FAU - Ashwell, K W AU - Ashwell KW FAU - Farnsworth, A E AU - Farnsworth AE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Surg JT - Cardiovascular surgery (London, England) JID - 9308765 RN - 0 (BAX protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (bcl-2-Associated X Protein) RN - 0 (fas Receptor) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) SB - IM MH - Aged MH - Apoptosis/*genetics MH - Caspase 3 MH - Caspases/genetics MH - Cell Death/*genetics MH - *Coronary Artery Bypass MH - Coronary Artery Disease/genetics/pathology/*surgery MH - Female MH - Gene Expression/physiology MH - Graft Occlusion, Vascular/*genetics/pathology MH - Humans MH - In Situ Nick-End Labeling MH - Male MH - Microscopy, Electron MH - Middle Aged MH - Necrosis MH - Proto-Oncogene Proteins/genetics MH - Proto-Oncogene Proteins c-bcl-2/genetics MH - Reoperation MH - Tumor Suppressor Protein p53/genetics MH - Veins/pathology/*transplantation MH - bcl-2-Associated X Protein MH - fas Receptor/genetics EDAT- 2001/06/23 10:00 MHDA- 2001/08/31 10:01 CRDT- 2001/06/23 10:00 PHST- 2001/06/23 10:00 [pubmed] PHST- 2001/08/31 10:01 [medline] PHST- 2001/06/23 10:00 [entrez] AID - S0967210900001253 [pii] AID - 10.1016/s0967-2109(00)00125-3 [doi] PST - ppublish SO - Cardiovasc Surg. 2001 Aug;9(4):319-28. doi: 10.1016/s0967-2109(00)00125-3.