Abstract 1714: Oleic And Palmitic Acid Interfere With The Inhibition Of Platelet Function And Thromboxane Formation By Aspirin: A Possible Mechanism Of Aspirin Resistance
Some fatty acids (FA) have limited anti-inflammatory effects due to a weak competition with arachidonic acid, the major substrate of cyclooxygenase (COX) enzymes. Since recent evidence has shown that nonsteroidal anti-inflammatory drugs can prevent aspirin from acetylating and inhibiting platelet COX-1, we have studied whether FA have a similar potential to interfere with platelet inhibition by aspirin. Platelet-rich plasma from healthy donors was pretreated with selected FA at biologically relevant concentrations (0.01–3 mmol/L). Aspirin (30 μmol/L) was then added and arachidonic acid-induced aggregation (turbidimetry) and thromboxane (TX) B2 formation (immunoassay) determined. The effect of FA on platelet function was also studied in the absence of aspirin. Further, we analysed the potential of FA for interaction with aspirin by measuring COX-1 activity in a cell-free system (COX-dependent luminol oxidation by platelet microsomes). Screening of saturated and unsaturated FA showed that oleic (18 :1n-9) and palmitic acid (16 :0, each 1 mmol/L) moderately inhibited arachidonic acid-induced platelet aggregation (75 ± 7 and 43 ± 18% of control, respectively, p < 0.05) with little inhibition of TX formation. These FA were further studied for interaction with platelet inhibition by aspirin. While 30 μmol/L aspirin completely prevented arachidonic acid-induced aggregation, this effect was largely abolished in the presence of oleic acid over a wide concentration range (0.01–3 mmol/L). Moreover, aspirin (30 μmol/L) decreased platelet TX formation to 2.4 ± 0.4% of control. Oleic acid also interfered with this inhibition (40 ± 5% at 1 mmol/l oleic acid, p < 0.01 vs aspirin alone). Similar results were obtained for palmitic acid. In platelet microsomal membranes, aspirin concentrations of 0.3–1 mmol/L were required for COX inhibition. Again, both studied FA preserved platelet COX activity in the presence of aspirin, confirming the interaction observed in intact platelets. In conclusion, oleic and palmitic acid interfere in vitro with the antiplatelet effect of aspirin. These FA are integral components of nutritional fats and dietary supplements. Extensive supply may interfere with aspirin in patients with cardiovascular disease.