Eskimo plasma constituents, dihomo-gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid inhibit the release of atherogenic mitogens.
Studies in man and laboratory animals suggest that omega 3 polyunsaturated fatty acid constituents 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 fibro-proliferative component of atherosclerotic plaques. Both 5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) and 4,7,10,13,16,19-docosahexaenoic acid (22:6 omega 3), 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 (18:3 omega 3), 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-gamma-linolenic acid (8,11,14-eicosatrienoic acid 20:3 omega 6), 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-gamma-linolenic acid precursor gamma-linolenic acid (18:3 omega 6) may exert antiatherosclerotic effects by inhibiting the release of mitogens from platelets and other cells.
Smith
D L
DL
Institute of Experimental Pharmacology, Syntex Palo Alto, CA 94303.
Willis
A L
AL
Nguyen
N
N
Conner
D
D
Zahedi
S
S
Fulks
J
J
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology*; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006131:Growth Inhibitors; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D004930:Inuit; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006131:Growth Inhibitors; D006133:Growth Substances; D010975:Platelet Aggregation Inhibitors; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D015126:8,11,14-Eicosatrienoic Acid