Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia.

摘要: Cholesteryl ester transfer protein (CETP) is a major determinant of plasma levels or nign-density lipoprotein-cholesterol (HDL-C) in humans. The anti-atherogenic effect lowering CETP dependent not only on HDL-C but also metabolic background increased low-density lipoprotein very-low-density lipoprotein. Here we investigated the effects JTT-705, chemical inhibitor CETP, development atherosclerosis Japanese white rabbits fed high cholesterol diet. After 4 weeks diet 0.25% cholesterol-containing chow, 100 mg/kg (low dose) 300 (high JTT-705 was given, and animals were monitored at 0, 4, 8 12. Aortic atherosclerotic lesions determined end this period. induced significant increase high-dose group [from 21 + 3 to 50 ± 7 mg/dl (mean S.E.M.); P < 0.0001] compared with control (from 2 27 mg/dl). atheromatous area 60 9% 58 group. Moreover, correlation analysis showed that triacylglycerol non-HDL-C had direct relationship atherosclerosis, activity did not. Thus alone have an our rabbit model, severe hypercholesterolaemia suggesting relatively minor HDL-elevating therapy as decreases (or triacylglycerol) patients hypercholesterolaemia, such familial hypercholesterolaemia.