Vascular endothelial over-expression of human soluble epoxide hydrolase (Tie2-sEH Tr) attenuates coronary reactive hyperemia in mice: Role of oxylipins and ω-hydroxylases

Ahmad Hanif, Matthew L. Edin, Darryl C. Zeldin, Christophe Morisseau, John R. Falck, Mohammed A. Nayeem

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: Epoxyeicosatrienoic acids (EETs) and omega-(ω)-Terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω-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). ω-Terminal HETEs are formed by ω-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 ω-hydroxylases, activation of PPARγ, 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 ω-hydroxylases and activation of PPARγ 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 ω-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 overexpression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARγ-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 ω-hydroxylases and activation of PPARγ enhance it.

Original languageEnglish (US)
Article number0169584
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

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Oxylipins
epoxide hydrolase
oxylipins
Epoxide Hydrolases
Hyperemia
Mixed Function Oxygenases
blood vessels
Blood Vessels
Hydroxyeicosatetraenoic Acids
mice
Peroxisome Proliferator-Activated Receptors
ischemia
acids
Acids
vasodilation
rosiglitazone
Chemical activation
Vasodilation
hyperemia
Ischemia

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vascular endothelial over-expression of human soluble epoxide hydrolase (Tie2-sEH Tr) attenuates coronary reactive hyperemia in mice : Role of oxylipins and ω-hydroxylases. / Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.; Nayeem, Mohammed A.

In: PLoS One, Vol. 12, No. 1, 0169584, 01.01.2017.

Research output: Contribution to journalArticle

Hanif, Ahmad ; Edin, Matthew L. ; Zeldin, Darryl C. ; Morisseau, Christophe ; Falck, John R. ; Nayeem, Mohammed A. / Vascular endothelial over-expression of human soluble epoxide hydrolase (Tie2-sEH Tr) attenuates coronary reactive hyperemia in mice : Role of oxylipins and ω-hydroxylases. In: PLoS One. 2017 ; Vol. 12, No. 1.
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