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

Arterioscler Thromb Vasc Biol

October 2016

From the Department of Pharmacology (J.Y., B.E.T., R.A., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Cardeza Foundation for Hematological Research, Thomas Jefferson University, Philadelphia, PA (J.Y., B.E.T., R.A., P.F.-P., J.Y., M.H.); and Department of Chemistry and Biochemistry, University of California Santa Cruz (A.R.G., C.J.F., T.R.H.).

Objective: 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 of polyunsaturated fatty acids remain controversial because of lack of mechanistic and in vivo evidence. We present direct evidence that an omega-6 polyunsaturated fatty acid, dihomo-γ-linolenic acid (DGLA), exhibits in vivo cardioprotection through 12-lipoxygenase (12-LOX) oxidation of DGLA to its reduced oxidized lipid form, 12(S)-hydroxy-8Z,10E,14Z-eicosatrienoic acid (12(S)-HETrE), inhibiting platelet activation and thrombosis.

Approach And Results: DGLA inhibited ex vivo platelet aggregation and Rap1 activation in wild-type mice, but not in mice lacking 12-LOX expression (12-LOX(-/-)).

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