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

To overcome the sand rats' resistance to cholesterol induced atherosclerosi s, animals were given D2 vitamin at 2000 IU/rat per day associated with cho lesterol-enriched diet for 45 days, following 45 days of high cholesterol d iet alone. At days 0, 45 and 90, plasma parameters, aortic and heart morpho logy were examined. Other animals receiving a high cholesterol diet alone w ere used as a control group. Results showed at day 45 severe hypercholester olemia, elevated plasma LDL and VLDL-cholesterol, oxidized LDL and calcium levels, a rise of lecithin cholesterol acyl transferase activity and modera te hyperinsulinemia. Lesions were characterized by widening of the first in terlamellar spaces in the aorta, fibrosis of coronary arterial wall and rec ent foci of myocardial fibrosis. At day 90, plasma calcium level decreased and oxidized LDL were more enhanced. Insulin resistance development was ass ociated with glucose intolerance and hyperinsulinemia. The D2 vitamin admin istration induced advanced atherosclerotic lesions in arterial wall, repres ented by the rupture of elastic lamellae, smooth muscle cell proliferation and lipid-calcic core. The complicated plaque frequently evolved into ulcer ations. The ischaemic effects were represented by acute myocardial infarcti on. D2 vitamin is an atherogenic agent which, when associated with hypercho lesterolemia, allows the development of advanced atherosclerotic lesions in sand rat which resembles human plaque. (C) 2000 Elsevier Science Ireland L td. All rights reserved.