12(S)-HETrE, a 12-Lipoxygenase Oxylipin of Dihomo-γ-Linolenic Acid, Inhibits Thrombosis via Gα s Signaling in Platelets

• DOI: 10.1161/atvbaha.116.308050
• Publication Date: 2016-07-29T03:33:00Z
• Authors: Jennifer Yeung; Benjamin E. Tourdot; Reheman Adili; Abigail R. Green; Cody J. Freedman; Pilar Fernandez-P...; Johnny Yu; Theodore R. Holman; Michael Holinstat
• Keywords: Arteriole; Ex vivo

Dietary supplementation with polyunsaturated fatty acids has been widely used for primary and secondary prevention of cardiovascular disease in individuals at risk; however, the cardioprotective benefits remain controversial because lack mechanistic vivo evidence. We present direct evidence that an omega-6 acid, dihomo-γ-linolenic acid (DGLA), exhibits cardioprotection through 12-lipoxygenase (12-LOX) oxidation DGLA to its reduced oxidized lipid form, 12(S)-hydroxy-8Z,10E,14Z-eicosatrienoic (12(S)-HETrE), inhibiting platelet activation thrombosis.DGLA inhibited ex aggregation Rap1 wild-type mice, but not mice lacking 12-LOX expression (12-LOX(-/-)). Similarly, treated were able reduce thrombus growth (platelet fibrin accumulation) after laser-induced injury arteriole cremaster muscle, 12-LOX(-/-) supporting a requirement mediating inhibitory effects on platelet-mediated formation. Platelet formation also suppressed when directly 12(S)-HETrE. Importantly, 2 hemostatic models, tail bleeding rupture showed no alteration hemostasis 12(S)-HETrE treatment. Finally, mechanism protection was shown be mediated via Gαs-linked G-protein-coupled receptor pathway human platelets.This study provides DGLA, inhibits injury-induced thrombosis oxylipin, 12(S)-HETrE, which strongly supports potential regulation function. Furthermore, this is first oxylipin regulating function Gs α subunit-linked receptor-dependent manner.