Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts

This study aimed to investigate the features of cell death occurring in aor tocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of >75% were explanted fr om 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibo dies 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 cel l death were examined by electron microscopy, Anti-apoptotic (Bcl-2) and pr o-apoptotic (Bax, p53, CPP32 and Pas) proteins were expressed throughout th e graft wall, but marked differences in the characteristics of cell death w ere noted between atherosclerotic and non-atherosclerotic areas of the inti ma, In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical feat ures of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic pr oteins showed no correlation with TUNEL. In contrast, in non-atheroscleroti c areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and p ro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In athero sclerotic areas, non-atherosclerotic intimal areas, and in the underlying m edia, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastr ucturally, apoptotic bodies and features of necrosis were observed in non-a therosclerotic areas of grafts. The present observations indicate that in a therosclerotic areas, cell death occurs mainly by necrosis, while in non-at herosclerotic areas, cell death occurs by both necrosis and apoptosis, An i mbalance between DNA fragmentation and DNA synthesis may contribute to graf t instability and failure. (C) 2001 The International Society for Cardiovas cular Surgery. Published by Elsevier Science Ltd. All rights reserved.