FOAM CELL REPLICATION AND SMOOTH-MUSCLE CELL APOPTOSIS IN HUMAN SAPHENOUS-VEIN GRAFTS

Occlusion of saphenous vein grafts is a major problem after coronary a rtery bypass grafting. Segments of occluded and suboccluded implanted aortocoronary grafts were obtained during re-intervention bypass graft ing in 47 patients yielding a total of 80 vein grafts. The grafts were studied by immunohistochemistry for smooth muscle cells (alpha-SMC ac tin), macrophages (HAM56), cell replication (PCNA, Ki-67) and transmis sion and scanning electronmicroscopy (TEM, SEM). In 81% of the examine d grafts the (sub)occlusion was due to a myo-intimal thickening and an associated luminal accumulation of foam cells and mural thrombi. The foam cells were constantly found at the luminal site of the myo-intima l thickening and within the luminal part of adherent thrombi. Transmis sion electronmicroscopy demonstrated phagocytosis of platelets and pla telet fragments by the foam cells. A significant fraction of the foam cells demonstrated nuclear immunoreactivity for Ki-67 and PCNA. The my o-intimal thickening of the vein grafts was composed of smooth muscle cells lying in a fibrous tissue matrix. The smooth muscle cells were s urrounded by prominent basal lamina and showed ultrastructural feature s of apoptosis. Our results support the hypothesis that phagocytosis o f lipid rich platelets by monocytes set up a mechanism for foam cell f ormation and replication in human saphenous vein grafts. The transform ation of a smooth muscle cell rich myo-intimal thickening towards a fi brous, cell poor intimal thickening could be induced by progressive sm ooth muscle cell loss through apoptosis.