Abstract
Abstract 2169
Platelets play a pivotal role in thrombotic events leading to clot formation and clot stability in vivo. Uncontrolled signaling events in the platelet can result in unwanted thrombosis, which may eventually lead to the development of myocardial infarction or stroke. Previously, we have shown that ex vivo treatment of human platelets with the ω-6 fatty acid dihomo-γ-linolenic acid (DGLA) or its eicosanoid derived from 12-LOX oxidation, 12-hydroxyeicosatrienoic acid (12(S)-HETrE), inhibits PAR and collagen-induced platelet aggregation, clot retraction, and GPIIbIIIa activation. Since early studies have shown dietary supplementation of fatty acids increase fatty acid incorporation into the platelet lipid membrane (Barre, DE Lipids 1992; 27(5): 315–320; Marry, MJ Prostaglandins Leukot Essent Fatty Acids 1997; 56(3):223–223), we postulated that altering fatty acid composition in the platelet through dietary supplementation in vivo may be a viable approach to inhibiting platelet function. Therefore, a longitudinal study of wild-type mice on normal chow compared to mice supplemented with high (.5 g/kg) or low (.13 g/kg) DGLA diets was conducted. Each set of mice (7–8 mice) was given the designated diet for a period of 1, 2, or 3 months. At each time point, tail bleeding times and ex vivo platelet function in PRP were performed. Tail bleeding times from mice on the high DGLA diet were significantly prolonged by more than 15 minutes. Further, a smaller but statistically significant delay in clotting time was observed in mice on the low DGLA diet compared with control mice. Additionally, ex vivo aggregation response to collagen (1 μg/mL to 20 μg/mL) and PAR4-AP (50 μM to 500 μM) in platelets from mice on the high DGLA diet showed significant shifts to the right in their ability to induce platelet aggregation compared with control mice suggesting these mice were protected against thrombosis. JON/A and P-selectin binding to the PRP of high and low DGLA were also significantly attenuated in response to PAR4-AP. This study, which evaluated the in vivo and ex vivo effects of DGLA on regulation of platelet reactivity, supports DGLA as a potent, endogenous anti-thrombotic agent. Understanding the mechanistic details by which DGLA protects against thrombosis and maintains hemostasis through its COX-1 and 12-LOX-dependent bioactive metabolites will help to identify the potential viability of this target for anti-platelet intervention.
Disclosures:
No relevant conflicts of interest to declare.
Suppression of Leukotriene B4 Generation by Ex-vivo Neutrophils Isolated from Asthma Patients on Dietary Supplementation with Gammalinolenic Acid-containing Borage Oil: Possible Implication in Asthma
