The role of cholesterol accumulation in prosthetic vascular graft anastomotic intimal hyperplasia

Abstract

To demonstrate that modulation of plasma cholesterol concentrations affects prosthetic vascular graft anastomotic intimal hyperplasia (AIH), aortic grafts were examined histologically and biochemically in 41 rabbits. Twenty-seven rabbits were fed standard rabbit diet, whereas 14 were fed cholesterol-supplemented diet to induce hypercholesterolemia. A smooth muscle cell proliferative response, similar to AIH in humans, was seen equally at the proximal and distal anastomoses. However, surface area and thickness of AIH were significantly greater in rabbits with hypercholesterolemia. Anastomotic tissue cholesterol concentrations were fifteenfold higher in rabbits with hypercholesterolemia than in rabbits with normal cholesterol concentrations and anastomotic cholesterol concentrations were fivefold higher than in the aorta away from the graft in rabbits with hypercholesterolemia. Preferential deposition of radioiodinated dilactitol tyramine coupled to low-density lipoproteins, but not albumin, was demonstrated in anastomotic areas and grafts of rabbits with normal cholesterol concentrations as well. Surface area and thickness of AIH correlated closely with plasma and tissue cholesterol concentrations. Oxidized products of lipoproteins have been shown to stimulate production of growth factors that cause smooth muscle cell proliferation, migration, and synthetic function. It is likely they play an important part in prosthetic vascular graft AIH, similar to their role in atherogenesis.