Impaired graft healing due to hypercholesterolemia is prevented by dietary supplementation with α-tocopherol

ObjectiveThe patency of prosthetic grafts is partly limited by incomplete endothelial cell coverage and development of anastomotic intimal hyperplasia. The goal of this study was to determine the effect of elevated cholesterol on prosthetic graft healing and the ability of α-tocopherol to improve healing.MethodsRabbits were placed on one of four diets: chow, chow plus 1% cholesterol, chow plus α-tocopherol, or chow plus 1% cholesterol and α-tocopherol. After 2 weeks, expanded polytetrafluoroethylene grafts (12-cm long, 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol and α-tocopherol content, endothelial coverage, anastomotic intimal thickness, and cellular composition of the neointima.ResultsAt the time of graft implantation, plasma cholesterol was 34 ± 4 mg/dL in the chow group and 689 ± 30 mg/dL in the 1% cholesterol group (P < .05). Grafts removed from hypercholesterolemic rabbits had marked intimal thickening, with an intima/graft thickness ratio of 0.76 ± 0.29 compared with 0.14 ± 0.06 in chow animals (P < .05). Macrophage infiltrate was increased to 45 ± 11 macrophages/0.625 mm2 in grafts from hypercholesterolemic rabbits compared with 0 ± 0.4 in controls (P < .05). Endothelialization of grafts was lower in hypercholesterolemic rabbits than in the chow group, with endothelial cells covering 46% ± 7% and 62% ± 7% of the graft surface, respectively (P = .05). When α-tocopherol was added to the 1% cholesterol diet, the macrophage count decreased to 12 ± 8, the intimal/graft thickness ratio decreased to 0.17 ± 0.09, and endothelial coverage increased to 70% ± 7% (P < .05 compared with the high-cholesterol group).ConclusionAnastomotic intimal hyperplasia is dramatically increased and endothelialization is reduced in rabbits on a high-cholesterol diet, but α-tocopherol supplementation blocks the augmented neointimal thickening and improves endothelial cell coverage.

Clinical RelevanceElevated cholesterol is associated with an increased inflammatory response, the development of intimal hyperplasia and reduced endothelialization after stent or prosthetic graft placement in animal models, and decreased graft patency in clinical studies. α-Tocopherol or other antioxidant, anti-inflammatory agents may be effective in lessening this pathologic response.