Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans

Polyunsaturated dietary fat (n−3 and n−6) results in less atherosclerosis in monkeys compared to lard (Parks, J.S., Kaduck‐Sawyer, J., Bullock, B.C., and Rudel, L.L.,Arteriosclerosis 10, 1102–1112; Rudel, L.L., Parks, J.S., Johnson, F.L., and Babiak, J.,J. Lipid Res. 27, 465–474, 1986). We hypothesized that this was due, in part, to a decreased reactivity of low density lipoproteins (LDL) with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys were fed diets containing lard, safflower oil (n−6 polyunsaturated; Poly), menhanden fish oil (FO), or oleic acid‐rich safflower oil (oleinate; Mono) for 14 mon, and plasma LDL were isolated and characterized. Several properties of LDL thought to be important in the interaction of LDL with arterial PG were measured including LDL particle size, chemical composition, sialic acid content, density distribution, apolipoprotein E (apoE) content and cholesteryl ester transition temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet consumption averaged (mean±SEM): FO (366±45), Lard (352±27), Poly (279±24), and Mono (230±43). The composition of LDL was similar among diet groups except that FO LDL were relatively depleted of cholesteryl ester and enriched in protein and were smaller in size. LDL sialic acid content was similar among diet groups (4.5–5.0 μg/mg LDL protein). The LDL apoE/B molar ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0±1.0), Poly (2.0±0.1), Lard (1.8±0.5), and FO (1.0±0.2). The FO group had a lower proportion (13%) of the apoE enriched d=1.015–1.025 g/mL subfraction of LDL than did the other diet groups (31–45%). The transition temperature of the LDL cholesteryl esters was below body temperature for the FO and Poly groups (36°C) and above for the Lard and Mono groups (40–44°C). The percentage of LDL cholesterol that formed insoluble complexes with arterial chondroitin sulfate PG averaged: Mono (29±4%), Lard (18±3%), Poly (14±3%), and FO (7±2%). Among all diet groups, there was a significant positive correlation (r=0.54) between LDL‐PG complex formation and LDL apoE/B molar ratio. We conclude that dietary FO and Poly result in LDL that are less reactive with arterial PG compared to Lard or Mono fats. While FO appears to decrease PG binding by decreasing the apoE content and amount of the largest LDL subfraction, Poly fat appears to affect LDL‐PG interactions by other mechanisms. Decreased LDL‐PG interactions may lead to decreased ath