Isomeric fatty acids and platelet function
1. Cis unsaturated fatty acids were shown to inhibit porcine platelet aggregation in response to both collagen and thrombin. Fatty acids with a trans double bond had an anti-aggregatory effect on collagen-induced aggregation but this was significantly less than that observed with the cis equivalent and was diminished as the dose of agonist increased. Thrombin-induced platelet aggregation was unchanged or slightly potentiated by trans isomers. 2. Both the cis and trans isomeric acids inhibited collagen-induced TXB2 production. The trans unsaturated fatty acids also inhibited TXB2 production in response to thrombin, even though they did not inhibit thrombin induced platelet aggregation. 3. Unlike arachidonic acid, the cis and trans mono-unsaturated fatty acids were not rapidly incorporated into membrane phospholipids but modified platelet aggregation whilst in the free acid form. 4. Pre-incubation of platelets with either cis or trans delta 13, 18:1, selectivity inhibited the incorporation of radio-labelled arachidonic acid into membrane PS. 5. Cis and trans unsaturated delta 13, 18:1, inhibited the initial turnover of membrane PI in response to thrombin possibly by an inhibitory effect on PI-specific phospholipase C. After 5 minutes, however, the level of arachidonic acid released from both PI and PE was increased in the presence of the isomeric fatty acids. This may have been via a potentiation of the action of phospholipase A2. 6. An increased release of arachidonic acid could result in the inhibition of aggregation if metabolised via the 12-lipoxygenase pathway, as the end products of this sytem have direct anti-aggregatory activity and inhibit the cyclo-oxygenase enzymes thus reducing TXA2 synthesis. 7. Cis unsaturated fatty acids, which produce a greater level of membrane disruption than the trans, may lead to more efficient channelling of the released arachidonic acid in the direction of the lipoxygenase pathway, and thereby produce a greater inhibition of aggregation. The possibility remains that the cis isomers have another, as yet unidentified mechanism by which they inhibit platelet aggregation.