Dietary polyunsaturated fat modifies low-density lipoproteins and reduces atherosclerosis of nonhuman primates with high and low diet responsiveness.

We tested the hypothesis that an increased content of n-6 polyunsaturated fatty acids (principally linoleic acid) in an atherogenic diet of nonhuman primates would decrease atherosclerosis by modifying the composition and decreasing the concentration of plasma low-density lipoprotein (LDL). A species readily susceptible to diet-induced atherosclerosis (cynomolgus monkey) was compared with a less-susceptible species (African green monkey) with dietary cholesterol concentration and saturated or polyunsaturated fat (40% of energy) as variables. In both species, cholesterol concentrations in whole plasma, LDL, and high-density lipoprotein (HDL) were 20-30% lower when polyunsaturated fat was fed, whereas dietary cholesterol increased LDL cholesterol three- to fourfold. LDL was enriched in cholesteryl oleate when saturated fat and cholesterol were fed. Dietary linoleic acid prevented cholesteryl oleate enrichment and promoted cholesteryl linoleate accumulation in LDL. At the same plasma cholesterol concentration, cynomolgus monkeys had higher LDL cholesterol and lower HDL-cholesterol concentrations than did African green monkeys. LDL particle size was significantly (P < 0.001) larger in the group of cynomolgus monkeys fed polyunsaturated fat but tended to be smaller in African green monkeys fed polyunsaturated fat. Dietary polyunsaturated fat protected against coronary artery atherosclerosis in both species. Thus, LDL particle size, per se, was not atherogenic; instead, coronary artery atherosclerosis and cholesteryl oleate enrichment of LDL were more highly correlated. This outcome suggests that information about LDL composition may be more important for understanding the pathogenesis of atherosclerosis than previously suspected.