Atherosclerosis in rabbit vein grafts

Abstract

Human coronary saphenous vein bypass grafts develop atherosclerosis more readily than do grafts made of internal mammary artery. The reasons for this increased susceptibility, particularly in the presence of hyperlipidemia, are not known. In this study in rabbits, we investigated the possibility that the increased susceptibility might be attributed to increased smooth muscle proliferation and foam cell accumulation in vein grafts compared to native artery. Hypercholesterolemic and control rabbits underwent placement of jugular vein grafts in the carotid artery. Dietary cholesterol content was adjusted to maintain serum cholesterol levels of 200 to 600 mg/dl in the fat-fed rabbits. The vein graft intimal thickness in hypercholesterolemic rabbits was greater than in normolipemic rabbits at 3 and 6 months after implant. The increased thickness in the hypercholesterolemic group was largely accounted for by an accumulation of lipid-laden macrophages. Medial thicknesses increased during the first month, remained constant at later times, and were similar in control and hypercholesterolemic animals. In both groups, endothelial and smooth muscle cell proliferation (thymidine labeling) increased immediately after graft implantation and declined at 3 and 6 months. No incremental mitogenic stimulus could be attributed to the hypercholesterolemia. In immunohistochemical preparations, the large foam cells were noted to be macrophages, and the intimal proliferating cells, to be smooth muscle. Proximal and distal carotid artery segments adjacent to the vein grafts in hypercholesterolemic rabbits had virtually no accumulation of lipid-laden macrophages. These results suggest that the endothelial and smooth muscle cell response in vein grafts adapting to the arterial circulation is not altered by hyperlipdemia, but that the wall becomes thick because of an accumulation of lipid-laden macrophages.