VITAMIN-E AND FATTY-ACID INTERVENTION DOES NOT ATTENUATE THE PROGRESSION OF ATHEROSCLEROSIS IN WATANABE HERITABLE HYPERLIPIDEMIC RABBITS

We investigated the effect of different interventions on aortic athero sclerosis in Watanabe rabbits. Four groups of rabbits were fed either an oleic acid-enriched diet (80% of total fat intake) with or without vitamin E supplementation (250 IU/kg) or a diet enriched in linoleic a cid with or without vitamin E supplementation for 6 months. At the sta rt of the study, plasma cholesterol concentration was 21.4+/-3.6 mmol/ L (n=32). The diets did not influence the mean plasma lipids and lipop rotein concentrations except for HDL cholesterol, which was increased more on the oleic acid-enriched diets than on the linoleic acid-enrich ed diets. Vitamin E levels in plasma and LDL were increased on the ole ic acid diet and reduced on the linoleic acid diet. On the latter diet , supplementation of vitamin E was quantitatively less effective in ra ising plasma or LDL vitamin E levels. The susceptibility of LDL to oxi dation was determined in vitro. Both oleic acid-enriched diets increas ed the lag time by 140% from baseline. The linoleic acid diet suppleme nted with vitamin E increased lag time by 59%. Linoleic acid alone, ho wever, decreased the lag time by 30%. Similar but inverse effects were seen on LDL oxidation rate. Thus, intervention protected LDL to oxida tion in the following order: oleic acid plus vitamin E>oleic acid>lino leic acid plus vitamin E>linoleic acid. Despite the differences in LDL oxidizability induced by the four experimental diets, assessment of a ortic atherosclerosis at the end of the 6-month dietary study period r evealed no differences among the four study groups. These results sugg est that a decrease in the oxidative susceptibility in vitro alone is not sufficient to attenuate atherogenesis when cholesterol levels rema in markedly elevated.