-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits

In this study, we asked the question “does -tocopherol supplementation prevent an increase in total plasma cholesterol (TPC) concentration and reduce the deposition of cholesterol in arterial plaques of rabbits fed atherogenic diets?” Isocaloric diets containing 0.1% cholesterol to induce atherosclerosis were enriched in one of three fats: saturated fats (SAT), monounsaturated fats (MONO), or n-6 polyunsaturated fats (POLY). Half of each of the three diets were supplemented with 2,500 IU -tocopherol/kg-diet. Unsupplemented diets contained 25 IU -tocopherol/kg-diet. Rabbits supplemented with -tocopherol had plasma -tocopherol concentrations 10-fold higher and an average TPC concentration 31% lower, P 0.017, than rabbits fed unsupplemented diets. Among the three fat-fed groups, the difference was greatest for the POLY fat fed group (54%, P 0.041). POLY fat-fed rabbits without -tocopherol supplementation had plasma HDL cholesterol concentrations that were less than half that of rabbits fed other fats, P 0.0001. In general, differences in mean esterified artery cholesterol concentrations among the three fat-fed groups, with and without -tocopherol supplementation, paralleled differences in TPC concentration among the groups. This study suggests that for rabbits fed high pharmacological doses of -tocopherol, atherosclerosis can be diminished in situations where the plasma cholesterol concentrations are also significantly lower. — Schwenke, D. C., L. L. Rudel, M. G. Sorci-Thomas, and M. J. Thomas. -Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits. J. Lipid Res. 2002. 43: 1927–1938. Supplementary key words -tocopherol • fatty acid • polyunsaturated fatty acid • saturated fatty acid • monounsaturated fatty acid • high density lipoprotein • lipoprotein Oxidation of LDL is thought to promote atherosclerosis and cardiovascular disease in humans (1). It should follow then that -tocopherol and saturated fats would retard in vitro oxidation of LDL (2–9). Thus, one might expect -tocopherol and a diet rich in saturated fats to reduce atherosclerosis by retarding the in vivo oxidation of LDL (10–17). However, in healthy subjects -tocopherol did not reduce markers of oxidative stress like urinary F 2 -isoprostanes (18), and in some cases actually increased the plasma concentration of F 2 -isoprostanes (19). It is also well known that in humans and animals, high levels of dietary polyunsaturated fatty acids (PUFAs) reduce HDL cholesterol (HDL-C) (13, 20, 21), a process that would further increase the risk of atherosclerosis. Therefore, an increased concentration of linoleate in the plasma lipids would be expected to correlate with an increased risk of coronary heart disease (CHD) (22–25). However, men having a higher concentration of linoleate in plasma or adipose lipids are reported to have a lower risk of CHD (26, 27). Both non-human primates and rabbits have been shown to develop less atherosclerosis when fed polyunsaturated fat-rich diets that increase the polyunsaturated fat content of plasma lipid (12, 28–30). Therefore, the relationships between the fatty acid composition of the diet, plasma lipoprotein concentrations, and the risk of atherosclerosis and CHD are not clear cut and the risk of disease may depend on the interaction between several metabolic variables. Several reviews of the literature have suggested that -tocopherol or other antioxidants may reduce atherosclerosis or CHD (14, 31–34). High levels of dietary -tocopherol have been associated with reduced CHD in several population studies of men and women (35–38). One clinical trial of cholesterol lowering also observed reduced atherosclerosis progression in men who chose to consume high Abbreviations: BHT, butylated hydroxytoluene; DTPA, diethylenetriaminepentaacetic acid; MONO, diet group fed a diet enriched with monounsaturated fats; POLY, diet group fed a diet enriched with polyunsaturated fats; SAT, diet group fed a diet enriched with saturated fats. 1 Current address: Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ 85012. 2 To whom correspondence should be addressed. e-mail: mthomas @wfubmc.edu Manuscript received 8 July 2002. Published, JLR Papers in Press, August 16, 2002. DOI 10.1194/jlr.M200261-JLR200 by gest, on A uust 8, 2017 w w w .j.org D ow nladed fom