B Cambier

Haptoglobin polymorphism, a genetic risk factor in coronary artery bypass surgery

Haptoglobin (Hp) 2-2 type has been associated with accumulation of atherosclerotic lesions in essential hypertension. The aim of this study was to investigate the relationship between Hp type and the extension of coronary lesions in 765 male patients who underwent coronary artery bypass grafting (CABG). In this group, relative Hp1 (0.418) and Hp2 (0.582) allele frequencies were comparable with those of the reference population. Candidate CABG patients with a Hp 2-2 type were overrepresented in the younger (< 45 years) age group (P < 0.05). Hp 2-2 patients needed more bypass grafts than Hp 1-1 patients (relative risk 1.92 95% C.I. 1.24-2.96). The Hp 2-2 type was overrepresented among victims of a previous acute myocardial infarction (P < 0.05) and among patients with a lower (< 45 years) age at infarction (P < 0.05). In patients who already underwent a previous CABG graft survival time was shortest in Hp 2-2 type (P < 0.05). Patients with a Hp 2-2 type more likely develop atherosclerotic lesions despite comparable serum lipid concentrations.

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 (ÉL‐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 myo‐intimal thickening towards a fibrous, cell poor intimal thickening could be induced by progressive smooth muscle cell loss through apoptosis.

The modulation of smooth muscle cell phenotype is an early event in human aorto-coronary saphenous vein grafts

The morphological changes in human vein grafts occurring in the first days after a coronary bypass operation (CBP) are rarely reported in the literature. Sections of aorto-coronary vein grafts from 11 patients who died during the first 10 days after a CBP were obtained at autopsy. The number of vein grafts per patient ranged from 1 to 4, yielding a total of 28 vein grafts. The early changes in the vein grafts have been studied by light microscopy, immunohistochemistry, transmission and scanning electron microscopy. The study demonstrates that soon after grafting, the vein wall is infiltrated by polymorphonuclear leucocytes (PMN). At 24 h the endothelium shows extensive desquamation. The massive migration of PMN through the venous wall occurs simultaneously with the endothelial damage. The circular layer of the media is severely damaged, resulting in a loss of smooth muscle cells (SMC). The remaining SMC in this layer show a change toward the synthetic phenotype and a reduced expression of α-smooth muscle actin. These early changes in the SMC function may initiate the process of fibrosis in the intima and the media of the vein grafts.