Critical evaluation of normotensive rats as models for hypercholesterolaemia-induced atherosclerosis

摘要

In view of recent findings describing atherosclerosis as an inflammatory disease, the objective of the present study was to re-evaluate critically the potential of normotensive Wistar rats to represent a model for diet-induced hypercholesterolaemia and the hypercholesterolaemia induced atherosclerosis. Fourty five-week-old male rats were randomly allocated into two groups (n=20) and fed two different diets for 12 weeks: I - control AIN-93G diet and II - hypercholesterolaemic (high-cholesterol, high-cholate) AIN-93G diet, containing cholesterol (1 g/100 g) and cholate (0.5 g/100 g). Serum lipid profile, plasma inflammatory markers and endothelial functions were examined after 0,4,8 and 12 weeks. In addition, the atherosclerotic lesions formation in the aorta was evaluated after 12 weeks. In contrast to the control animals, the rats fed the hypercholesterolaemic diet had an elevated concentration of total serum cholesterol (2.05 vs 7.97 mmol/L) and LDL-cholesterol (0.63 vs 6.80 mmol/L). At the same time, the hypercholesterolaemic diet only slightly decreased serum HDL-cholesterol and had no effect on triglicerides. The hypercholesterolaemic diet, compared with the control diet, increased mildly plasma proinflammatory interleukin-6 concentrations (2.68 vs 4.85 pg/ml) whereas plasma C-reactive protein concentrations were below the detection limit (<0.01 pg/ml). The relaxation concentration curves to acetylcholine (to test endothelium-dependent relaxation) were not impaired in rats fed the hypercholesterolaemic diet. Also, the hypercholesterolaemic diet did not induce atherosclerotic lesion formation in the aortas of rats. In conclusion, diet-induced hypercholesterolaemia in normotensive rats induces only mild inflammatory process of the endotheliumbut it does not affect endothelial functions. Consequently, diet-induced hypercholesterolaemia does not lead to progression of atherosclerosis in rats thus invalidating the use of these animals as models for studies on hypercholesterolaemia-induced atherosclerosis.