Chemistry is the experimental and theoretical study of materials on their properties at both the macroscopic and microscopic levels. 23426-63-3, Name is Methyl 2-bromo-2-methylpropanoate, molecular formula is C5H9BrO2. In an article, author is Yamaguchi, Adriana,once mentioned of 23426-63-3, Product Details of 23426-63-3.
DHA 12-LOX-derived oxylipins regulate platelet activation and thrombus formation through a PKA-dependent signaling pathway
Background The effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding of how this omega-3 polyunsaturated fatty acid (omega-3 PUFA) regulates platelet reactivity and the subsequent risk of a thrombotic event is warranted. In platelets, DHA is oxidized by 12-lipoxygenase (12-LOX) producing the oxidized lipids (oxylipins) 11-HDHA and 14-HDHA. We hypothesized that 12-LOX DHA-oxylipins may be involved in the beneficial effects observed in dietary supplemental treatment with omega-3 PUFAs or DHA itself. Objectives To determine the effects of DHA, 11-HDHA, and 14-HDHA on platelet function and thrombus formation, and to elucidate the mechanism by which these omega-3 PUFAs regulate platelet activation. Methods and results DHA, 11-HDHA, and 14-HDHA attenuated collagen-induced human platelet aggregation, but only the oxylipins inhibited IIb beta 3 activation and decreased -granule secretion. Furthermore, treatment of whole blood with DHA and its oxylipins impaired platelet adhesion and accumulation to a collagen-coated surface. Interestingly, thrombus formation was only diminished in mice treated with 11-HDHA or 14-HDHA, and mouse platelet activation was inhibited following acute treatment with these oxylipins or chronic treatment with DHA, suggesting that under physiologic conditions, the effects of DHA are mediated through its oxylipins. Finally, the protective mechanism of DHA oxylipins was shown to be mediated via activation of protein kinase A. Conclusions This study provides the first mechanistic evidence of how DHA and its 12-LOX oxylipins inhibit platelet activity and thrombus formation. These findings support the beneficial effects of DHA as therapeutic intervention in atherothrombotic diseases.
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