Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB): Role of adenosine A2A receptor and plasma oxylipins

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Coronary reactive hyperemia (CRH) protects the heart against ischemia. Adenosine A2AAR–deficient (A2AAR−/−) mice have increased expression of soluble epoxide hydrolase (sEH); the enzyme responsible for breaking down the cardioprotective epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). sEH–inhibition enhances CRH, increases EETs, and modulates oxylipin profiles. We investigated the changes of oxylipins and their impact on CRH in A2AAR−/− and wild type (WT) mice. We hypothesized that the attenuated CRH in A2AAR−/− mice is mediated by changes in oxylipin profiles, and that it can be reversed by either sEH- or ω-hydroxylases–inhibition. Compared to WT mice, A2AAR−/− mice had attenuated CRH and changed oxylipin profiles, which were consistent between plasma and heart perfusate samples, including decreased EET/DHET ratios, and increased hydroxyeicosatetraenoic acids (HETEs). Plasma oxylipns in A2AAR−/− mice indicated an increased proinflammatory state including increased ω-terminal HETEs, decreased epoxyoctadecaenoic/dihydroxyoctadecaenoic acids (EpOMEs/DiHOMEs) ratios, increased 9-hydroxyoctadecadienoic acid, and increased prostanoids. Inhibition of either sEH or ω-hydroxylases reversed the reduced CRH in A2AAR−/− mice. In WT and sEH−/− mice, blocking A2AAR decreased CRH. These data demonstrate that A2AAR–deletion was associated with changes in oxylipin profiles, which may contribute to the attenuated CRH. Also, inhibition of sEH and ω-hydroxylases reversed the reduction in CRH.

Original languageEnglish (US)
Pages (from-to)83-95
Number of pages13
JournalProstaglandins and Other Lipid Mediators
Volume131
DOIs
StatePublished - Jul 1 2017

Fingerprint

Oxylipins
Adenosine A2A Receptors
Epoxide Hydrolases
Hyperemia
Hydroxyeicosatetraenoic Acids
Plasmas
Mixed Function Oxygenases
Acids
Adenosine
Prostaglandins
4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid
Enzymes
Ischemia

Keywords

  • Adenosine A receptor
  • Coronary reactive hyperemia
  • Heart perfusate oxylipins
  • Plasma oxylipins
  • Soluble epoxide hydrolase
  • ω-hydroxylases

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Pharmacology
  • Cell Biology

Cite this

Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB) : Role of adenosine A2A receptor and plasma oxylipins. / Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.; Ledent, Catherine; Tilley, Stephen L.; Nayeem, Mohammed A.

In: Prostaglandins and Other Lipid Mediators, Vol. 131, 01.07.2017, p. 83-95.

Research output: Contribution to journalArticle

Hanif, Ahmad ; Edin, Matthew L. ; Zeldin, Darryl C. ; Morisseau, Christophe ; Falck, John R. ; Ledent, Catherine ; Tilley, Stephen L. ; Nayeem, Mohammed A. / Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB) : Role of adenosine A2A receptor and plasma oxylipins. In: Prostaglandins and Other Lipid Mediators. 2017 ; Vol. 131. pp. 83-95.
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abstract = "Coronary reactive hyperemia (CRH) protects the heart against ischemia. Adenosine A2AAR–deficient (A2AAR−/−) mice have increased expression of soluble epoxide hydrolase (sEH); the enzyme responsible for breaking down the cardioprotective epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). sEH–inhibition enhances CRH, increases EETs, and modulates oxylipin profiles. We investigated the changes of oxylipins and their impact on CRH in A2AAR−/− and wild type (WT) mice. We hypothesized that the attenuated CRH in A2AAR−/− mice is mediated by changes in oxylipin profiles, and that it can be reversed by either sEH- or ω-hydroxylases–inhibition. Compared to WT mice, A2AAR−/− mice had attenuated CRH and changed oxylipin profiles, which were consistent between plasma and heart perfusate samples, including decreased EET/DHET ratios, and increased hydroxyeicosatetraenoic acids (HETEs). Plasma oxylipns in A2AAR−/− mice indicated an increased proinflammatory state including increased ω-terminal HETEs, decreased epoxyoctadecaenoic/dihydroxyoctadecaenoic acids (EpOMEs/DiHOMEs) ratios, increased 9-hydroxyoctadecadienoic acid, and increased prostanoids. Inhibition of either sEH or ω-hydroxylases reversed the reduced CRH in A2AAR−/− mice. In WT and sEH−/− mice, blocking A2AAR decreased CRH. These data demonstrate that A2AAR–deletion was associated with changes in oxylipin profiles, which may contribute to the attenuated CRH. Also, inhibition of sEH and ω-hydroxylases reversed the reduction in CRH.",
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T2 - Role of adenosine A2A receptor and plasma oxylipins

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AU - Edin, Matthew L.

AU - Zeldin, Darryl C.

AU - Morisseau, Christophe

AU - Falck, John R.

AU - Ledent, Catherine

AU - Tilley, Stephen L.

AU - Nayeem, Mohammed A.

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