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Atherosclerosis in rabbit vein grafts
R M Zwolak1, T R Kirkman, A W Clowes
1University of Washington School of Medicine, Department of Surgery, Seattle 98195.
Summary
Vein grafts in hyperlipidemic rabbits showed increased intimal thickness due to lipid-laden macrophages, not smooth muscle cell proliferation. This suggests hyperlipidemia exacerbates atherosclerosis in vein grafts via macrophage accumulation.
Area of Science:
- Vascular Biology
- Atherosclerosis Research
- Surgical Grafting
Background:
- Human coronary artery bypass grafts using saphenous veins are more prone to atherosclerosis than internal mammary artery grafts.
- The specific reasons for this increased susceptibility, especially in hyperlipidemic conditions, remain unclear.
Purpose of the Study:
- To investigate if increased smooth muscle cell proliferation and foam cell accumulation in vein grafts contribute to their heightened susceptibility to atherosclerosis compared to native arteries.
- To assess the impact of hyperlipidemia on vein graft intimal and medial thickness, and cellular proliferation.
Main Methods:
- Jugular vein grafts were implanted into the carotid arteries of hypercholesterolemic and control rabbits.
- Dietary cholesterol was manipulated to achieve serum cholesterol levels of 200-600 mg/dl in hypercholesterolemic rabbits.
- Histological analysis, thymidine labeling for cell proliferation, and immunohistochemistry were used to evaluate graft changes at 3 and 6 months.
Main Results:
- Vein grafts in hypercholesterolemic rabbits exhibited greater intimal thickness at 3 and 6 months compared to normolipemic rabbits.
- This increased thickness was primarily due to the accumulation of lipid-laden macrophages.
- Smooth muscle cell proliferation increased post-implantation but was not further stimulated by hypercholesterolemia.
Conclusions:
- Hyperlipidemia contributes to vein graft atherosclerosis by promoting the accumulation of macrophages within the intima.
- Smooth muscle cell proliferation is not the primary driver of increased vein graft atherosclerosis in hyperlipidemic states.
- These findings highlight the role of lipid metabolism and inflammatory cell infiltration in vein graft disease.