The influence of the combined presence of diabetes mellitus and hypercholesterolaemia on the function and morphology of experimental vein grafts

Abstract

Diabetes and hypercholesterolaemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the combined effect of diabetes for 12 weeks (alloxan-induced) and hypercholesterolaemia for 8 weeks (1% cholesterol diet) on the formation of intimal hyperplasia and the vasomotor function of vein grafts. MATERIALS AND DESIGN: Thirty-two New Zealand White rabbits underwent a carotid vein bypass graft. Eight were controls, eight were diabetic, eight were hypercholesterolaemic and eight had both diabetes and hypercholesterolaemia. All vein grafts were harvested at 4 weeks postoperatively for morphology (n = 4) or contractility studies (n = 4). Compared to controls, both diabetes and hypercholesterolaemia increased intimal thickness by 20% and 63% respectively; medial thicknesses of these vein grafts were unchanged compared to control. In contrast, diabetes with hypercholesterolaemia dramatically increased intimal and medial thickness (1.8 fold and 1.6 fold respectively, compared to control). Smooth muscle cell contractility was enhanced in both the diabetic and hypercholesterolaemic groups. The presence of diabetes with hypercholesterolaemia did not further alter the enhanced smooth muscle cell contractile responses. This study suggests that the combination of both the atherogenic risk factors, hypercholesterolaemia and diabetes, significantly augments the formation of intimal hyperplasia in experimental vein grafts.