Eskimo plasma constituents, dihomo‐γ‐linolenic acid, eicosapentaenoic acid and docosahexaenoic acid inhibit the release of atherogenic mitogens

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Abstract
Studies in man and laboratory animals suggest that ω3 polyunsaturated fatty acid consituents of fish oils have antiatherosclerotic properties. We have studied the effects of several such polyunsaturated fatty acids for ability to modify the in vitro release of mitogens from human platelets. Such mitogens may produce the fibroproliferative component of atherosclerotic plaques. Both 5,8,11,14,17‐eicosapentaenoic acid (20∶5ω3) and 4,7,10,13,‐16,19‐docosahexaenoic acid (22∶6ω3), major constituents of fish oils, inhibited adenosine diphosphate‐induced aggregation of platelets and the accompanying release of mitogens. These effects are dose dependent. Linolenic acid (18∶3ω3), the biosynthetic precursor of eicosapentaenoic acid, also inhibited platelet aggregation and mitogen release. Eicosapentaenoic acid also inhibited mitogen release from human monocyte‐derived macrophages, which, in vivo, are an additional source of mitogens during atherogenesis. Potent inhibition of human platelet aggregation and mitogen release was also seen with dihomo‐γ‐linolenic acid (8,11,14‐eicosatrienoic acid 20∶3ω6), whose levels are reportedly elevated in Eskimos subsisting on marine diets. We conclude that diets that elevate plasma and/or tissue levels of eicosapentaenoic acid, docosahexaenoic acid and dihomo‐γ‐linolenic acid precursor γ‐linolenic acid (18∶3ω6) may exert antiatherosclerotic effects by inhibiting the release of mitogens from platelets and other cells.