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We examined the effect of isocaloric substitution of dietary fish oil for lard on the properties of low density lipoproteins (LDL) important in binding to arterial proteoglycans (PG). Cynomolgus monkeys (n = 10) were fed atherogenic diets enriched in fish oil or lard in a crossover study consisting of two 15-week phases of atherogenic diet separated by a 6-week monkey chow "wash-out period." LDL were isolated from plasma during each dietary phase, characterized for chemical and physical properties, and assessed for their ability to interact in vitro with arterial PG. Plasma LDL cholesterol was similar during fish oil and lard consumption (356 +/- 34 and 331 +/- 17 mg/dl, mean +/- SEM), but during fish-oil feeding relative to that of lard, LDL size was smaller (4.2 +/- 0.1 versus 4.9 +/- 0.1 g/mumol) and LDL particles differed in chemical composition. When animals were fed fish oil, significantly fewer (p less than 0.05) LDL particles bound to PG in both dietary phases: 1.00 +/- 0.27 (x10(12)) versus 5.31 +/- 0.83 (x10(12)) particles/micrograms PG in phase 1 and 3.56 +/- 0.67 (x10(12)) versus 6.00 +/- 0.52 (x10(12)) in phase 2 for LDL from animals fed fish oil and lard, respectively. These studies indicate that dietary fat-induced changes in LDL particles lead to altered in vitro interactions with artery wall PG and suggest a novel mechanism for the protective effect of fish oil against atherosclerosis.

Reduced proteoglycan binding of low density lipoproteins from monkeys (Macaca fascicularis) fed a fish oil versus lard diet.