Expression of vascular endothelial growth factor in aortocoronary saphenous vein bypass grafts

Neovascularisation is a prominent feature of long-term aortocoronary saphen ous vein bypass grafts but mechanisms involved in the formation of neovesse ls have not been previously studied. Vascular Endothelial Growth Factor (VE GF) is an important angiogenic factor that induces migration and proliferat ion of endothelial cells, enhances permeability and modulates thrombogeneci ty. This study investigated the expression of VEGF in aortocoronary sapheno us vein bypass grafts. Aortocoronary saphenous vein bypass grafts with angi ographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. The grafts demonstrated two distinct forms of graft occlusion: four out of the 14 graft occlusions (29%) resulted fro m severe hyperplastic transformation of the intima complicated by thrombi ; attached to the degenerating liminal endothelium; the remaining graft occlu sions (71%) were due to the development of atherosclerotic lesions associat ed with mural thrombosis. Hiperplastically altered intimal segments were pr actically free of neovascularisation while atherosclerotic-like lesions con tained neovessels irregularly distributed throughout. Intimal neovessels we re located exclusively in microzones enriched with VEGF-expressing cells an d, furthermore, neovascular endothelial cells themselves also displayed VEG F immunopositivity. Double-immunostaining revealed that in areas of neovasc ularisation. the vast majority macrophages (CD68+) expressed VEGF. Some CD6 8+ foam cells that surrounded branches of neovascularisation were also VEGF -positive. These findings suggest that VEGF expressed by neovascular endoth elial cells and by macrophages may act as a local regulator of endothelial cells functions and may induce intimal neovascularisation in aortocoronary saphenous vein bypass grafts affected by atherosclerosis. (C) 2001 The Inte rnational Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved.