DHA 12-LOX-derived oxylipins regulate platelet activation and thrombus formation through a PKA-dependent signaling pathway.

摘要: Background The effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding how this omega-3 polyunsaturated fatty (ω-3 PUFA) regulates platelet reactivity the subsequent risk thrombotic event is warranted. In platelets, DHA oxidized by 12-lipoxygenase (12-LOX) producing lipids (oxylipins) 11-HDHA 14-HDHA. We hypothesized that 12-LOX DHA-oxylipins may be involved in beneficial observed dietary supplemental treatment with ω-3 PUFAs or itself. Objectives To determine DHA, 11-HDHA, 14-HDHA function thrombus formation, to elucidate mechanism which these regulate activation. Methods results attenuated collagen-induced human aggregation, but only oxylipins inhibited ⍺IIbβ3 activation decreased ⍺-granule secretion. Furthermore, whole blood its impaired adhesion accumulation collagen-coated surface. Interestingly, formation was diminished mice treated 14-HDHA, mouse following acute chronic suggesting under physiologic conditions, mediated through oxylipins. Finally, protective shown via protein kinase A. Conclusions This study provides first evidence inhibit activity formation. These findings support as therapeutic intervention atherothrombotic diseases.