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The hypothesis that n-3 fatty acid incorporation into low-density lipoprotein (LDL) particles renders them more susceptible to oxidative modification and possibly more atherogenic was tested using two groups of female Yucatan miniature swine (10 animals per group) fed an atherogenic diet for 8 months. As a supplement to the atherogenic diet, the first group received a daily oral dose of the fish oil (FO) concentrate MaxEPA, rich in n-3 fatty acids, while the second group received the same dosage of a control oil (CO) low in n-3 fatty acids but with the same ratio of polyunsaturated to monounsaturated to saturated fatty acids as MaxEPA. At 8 months, the animals were killed and perfusion fixed, and all major vessels were removed for morphological assessment of atherosclerotic lesion area. Before fixation, blood samples were collected from all 20 pigs, and LDL (d = 1.019 to 1.063 g/mL) was separated from the plasma by ultracentrifugation. A series of in vitro oxidative modification reactions were carried out by incubating the LDL with a copper sulfate solution. The susceptibility of each LDL preparation to oxidation was determined by measuring both the formation of conjugated dienes and the relative mobility of each sample in an agarose gel. The incorporation of n-3 fatty acids into LDL particles decreased the lag phase by 30%, resulting in an increased mobility of FO-LDL (compared with CO-LDL) when incubated for 0.5 to 12 hours, but at longer incubation times (18 to 24 hours), the extent of modification between the two groups became equal.(ABSTRACT TRUNCATED AT 250 WORDS)

n-3 fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo.