Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and ω-Hydroxylases.

摘要: Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(ω)-terminal hydroxyeicosatetraenoic (HETEs). EETs have numerous beneficial physiological effects, including vasodilation protection against ischemia/reperfusion injury, whereas ω-terminal HETEs induce vasoconstriction vascular dysfunction. We evaluated the effect of these on post-ischemic known as coronary reactive hyperemia (CRH). CRH prevents potential harm associated transient ischemia. The effects are reduced after their hydrolysis to dihydroxyeicosatrienoic (DHETs) by soluble epoxide hydrolase (sEH). formed ω-hydroxylase family members. relationship among endothelial over-expression sEH (Tie2-sEH Tr), changes in it may produce, pharmacologic inhibition ω-hydroxylases, activation PPARγ, response a brief ischemia is not known. hypothesized that attenuated isolated mouse hearts through modulation oxylipin profiles, both ω-hydroxylases PPARγ enhance CRH. Compared WT mice, Tie2-sEH Tr mice had decreased CRH, repayment volume, duration, repayment/debt ratio (P < 0.05), increased same parameters mice. Inhibition t-AUCB reversed Endothelial significantly changed decreases DHETs, mid-chain HETEs, prostaglandins 0.05). Treatment rosiglitazone, PPARγ-agonist, enhanced 0.05) wild type (WT) These data demonstrate (through changing profiles) attenuates it.