New model of atherosclerosis in insulin resistant sand rats:: hypercholesterolemia combined with D2 vitamin

To overcome the sand rats' resistance to cholesterol induced atherosclerosis, animals were given D2 vitamin at 2000 IU/rat per day associated with cholesterol-enriched diet for 45 days, following 45 days of high cholesterol diet alone. At days 0, 45 and 90, plasma parameters, aortic and heart morphology were examined. Other animals receiving a high cholesterol diet alone were used as a control group. Results showed at day 45 severe hypercholesterolemia, elevated plasma LDL and VLDL-cholesterol, oxidized LDL and calcium levels, a rise of lecithin cholesterol acyl transferase activity and moderate hyperinsulinemia. Lesions were characterized by widening of the first interlamellar spaces in the aorta, fibrosis of coronary arterial wall and recent foci of myocardial fibrosis. At day 90, plasma calcium level decreased and oxidized LDL were more enhanced. Insulin resistance development was associated with glucose intolerance and hyperinsulinemia. The D2 vitamin administration induced advanced atherosclerotic lesions in arterial wall, represented by the rupture of elastic lamellae, smooth muscle cell proliferation and lipid-calcic core. The complicated plaque frequently evolved into ulcerations. The ischaemic effects were represented by acute myocardial infarction. D2 vitamin is an atherogenic agent which, when associated with hypercholesterolemia, allows the development of advanced atherosclerotic lesions in sand rat which resembles human plaque. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.