Albumin-bound docosahexaenoic acid and collagen-induced human platelet reactivity.
An in vitro system designed to mimic the effect of various plasma nonesterified (polyunsaturated) fatty acids on platelet function and metabolism was employed. Human platelet aggregation induced by submaximal (1.8 micrograms/ml) collagen stimulation was significantly inhibited by 2 min preincubation with 20 microM albumin-bound docosahexaenoic acid (22:6n-3) (DHA), but not by the other fatty acids tested. [3H]Phosphatidic acid (PA) formation, an indicator of phospholipase C activation following platelet stimulation, was moderately inhibited by eicosapentaenoic acid (20:5n-3), 11,14,17-eicosatrienoic acid (20:3n-3), dihomo-gamma-linolenic acid (20:3n-6), as well as DHA, but not by arachidonic acid (20:4n-6); this inhibition of phospholipase C activation could not explain the differential effect of DHA on platelet aggregation. The decreased production of thromboxane A2 (TxA2), as assessed by [3H]12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation, may account for the inhibition of collagen-induced aggregation by 20 microM DHA. Surprisingly, preincubation with 40 microM albumin-bound DHA, even though resulting in greater inhibition of collagen-induced aggregation, had less impact on HHT formation. A small but significant increase in [3H]prostaglandin D2 (PGD2) levels following 3-min collagen stimulation may have contributed to the greater antiaggregatory effect of 40 muM DHA. It is concluded that increased plasma nonesterified DHA may contribute to the dampened platelet activation and altered metabolism following fish oil supplementation of the diet.
Gaudette
D C
DC
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Holub
B J
BJ
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D010712:Phosphatidic Acids / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism*; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D010738:Type C Phospholipases / Q000097:blood
D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D010712:Phosphatidic Acids; D010975:Platelet Aggregation Inhibitors; D012709:Serum Albumin; D004281:Docosahexaenoic Acids; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003094:Collagen; D015118:Eicosapentaenoic Acid; D010738:Type C Phospholipases; D015230:Prostaglandin D2