Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts.
Occlusion of saphenous vein grafts is a major problem after coronary artery bypass grafting. Segments of occluded and suboccluded implanted aortocoronary grafts were obtained during re-intervention bypass grafting in 47 patients yielding a total of 80 vein grafts. The grafts were studied by immunohistochemistry for smooth muscle cells (alpha-SMC actin), macrophages (HAM56), cell replication (PCNA, Ki-67) and transmission and scanning electronmicroscopy (TEM, SEM). In 81% of the examined 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-intimal thickening and within the luminal part of adherent thrombi. Transmission electronmicroscopy demonstrated phagocytosis of platelets and platelet fragments by the foam cells. A significant fraction of the foam cells demonstrated nuclear immunoreactivity for Ki-67 and PCNA. The myo-intimal thickening of the vein grafts was composed of smooth muscle cells lying in a fibrous tissue matrix. The smooth muscle cells were surrounded by prominent basal lamina and showed ultrastructural features of apoptosis. Our results support the hypothesis that phagocytosis of lipid rich platelets by monocytes set up a mechanism for foam cell formation and replication in human saphenous vein grafts. The transformation of a smooth muscle cell rich myointimal thickening towards a fibrous, cell poor intimal thickening could be induced by progressive smooth muscle cell loss through apoptosis.
Department of Pathology, General Hospital Middelheim, Antwerp, Belgium.
M M
MM
Kockx
B A
BA
Cambier
H E
HE
Bortier
G R
GR
De Meyer
S C
SC
Declercq
P A
PA
van Cauwelaert
J
J
Bultinck
D017209:Apoptosis; D002455:Cell Division; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005487:Foam Cells / Q000737:chemistry / Q000166:cytology* / Q000648:ultrastructure; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012501:Saphenous Vein / Q000166:cytology / Q000637:transplantation*; D013927:Thrombosis / Q000473:pathology; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000648:ultrastructure
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen