Bypass graft disease: Analysis of proliferative activity in human aorto-coronary bypass grafts

Background: Aortocoronary bypass graft disease with its increasing clinical signification represents an unsolved problem in cardiological and heart surgery practice. Late occlusion of autologous saphenous vein grafts occurs against a background of medial and neointimal thickening due to migration and proliferation of smooth muscle cells and the later appearance of atherosclerotic plaques. To clarify the role of cellular proliferation in humans we characterized the cellular composition and proliferative index in 30 stenotic saphenous vein grafts. Methods: 30 stenotic vein grafts and 25 control veins were explantated during redo heart surgery procedures. Time between initial surgical intervention and explantation was 3-168 month (mean 94,8 month). The total area and cell count of the neointima, media and adventitia was calculated computer assisted. Actively proliferating cells were identified using antibody to Ki-67 and by double-lable immuncytochemistry with SMC actin, CD 31 (endothelial cells), CD 68 (makrophages) and CD 45 (T-lymphocytes). Results: Active proliferation was detected in different cell typs with a mean proliferation index of 0.15% ,0.18% and 0.086% for the neointima, media and adventita. Only 9% of the proliferating cells in the neointima were SMC (not identified cells 40%); corresponding 14% SMC (not identified cells 33%) were detected in the media. Endothelial cells were the predominante proliferating cell type in all sites of the vessel wall. Conclusion: 1. Proliferation occured at low level. While proliferation may play an important role in early lesions our data imply low proliferation activity in advanced graft lesions. Other mechanism like production and deposition of extracellular matrix (ECM) in the neointima are responsible for the lumen reduction of bypass grafts. 2. The high portion of unidentified cells may represent SMC or other cell types at different stages of differentiation; this requires further investigation. 3. The identification of proliferating macrophages and T-lymphocytes implicate an inflammatory component in the development of human bypass graft lesions.