| Title : Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and omega-Hydroxylases - Hanif_2017_PLoS.One_12_e0169584 |
| Author(s) : Hanif A , Edin ML , Zeldin DC , Morisseau C , Falck JR , Nayeem MA |
| Ref : PLoS ONE , 12 :e0169584 , 2017 |
| Abstract : Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(omega)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas omega-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the potential harm associated with transient ischemia. The beneficial effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). omega-terminal HETEs are formed by omega-hydroxylase family members. The relationship among endothelial over-expression of sEH (Tie2-sEH Tr), the changes in oxylipins it may produce, the pharmacologic inhibition of omega-hydroxylases, activation of PPARgamma, and CRH response to a brief ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse hearts with endothelial sEH over-expression through modulation of oxylipin profiles, whereas both inhibition of omega-hydroxylases and activation of PPARgamma enhance CRH. Compared to WT mice, Tie2-sEH Tr mice had decreased CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), whereas inhibition of omega-hydroxylases increased these same CRH parameters in Tie2-sEH Tr mice. Inhibition of sEH with t-AUCB reversed the decreased CRH in Tie2-sEH Tr mice. Endothelial over-expression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARgamma-agonist, enhanced CRH (P < 0.05) in both Tie2-sEH Tr and wild type (WT) mice. These data demonstrate that endothelial over-expression of sEH (through changing the oxylipin profiles) attenuates CRH, whereas inhibition of omega-hydroxylases and activation of PPARgamma enhance it. |
| ESTHER : Hanif_2017_PLoS.One_12_e0169584 |
| PubMedSearch : Hanif_2017_PLoS.One_12_e0169584 |
| PubMedID: 28056085 |
| Gene_locus related to this paper: human-EPHX2 |
| Gene_locus related to this paper: human-EPHX2 |
Hanif A, Edin ML, Zeldin DC, Morisseau C, Falck JR, Nayeem MA (2017)
Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and omega-Hydroxylases
PLoS ONE
12 :e0169584
Hanif A, Edin ML, Zeldin DC, Morisseau C, Falck JR, Nayeem MA (2017)
PLoS ONE
12 :e0169584