Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids

Neal L. Weintraub, Xiang Fang, Terry L. Kaduce, Mike VanRollins, Papri Chatterjee, Arthur A. Spector

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Cytochrome P-450-derived epoxyeicosatrienoic acids (EETs) are avidly incorporated into and released from endothelial phospholipids, a process that results in potentiation of endothelium-dependent relaxation. EETs are also rapidly converted by epoxide hydrolases to dihydroxyeicosatrienoic acid (DHETs), which are incorporated into phospholipids to a lesser extent than EETs. We hypothesized that epoxide hydrolases functionally regulate EET incorporation into endothelial phospholipids. Porcine coronary artery endothelial cells were treated with an epoxide hydrolase inhibitor, 4- phenylchalcone oxide (4-PCO, 20 μmol/l), before being incubated with 3H- labeled 14,15-EET (14,15-[3H]EET). 4-PCO blocked conversion of 14,15-[3H] EET to 14,15-[3H]DHET and doubled the amount of radiolabeled products incorporated into cell lipids, with >80% contained in phospholipids. Moreover, pretreatment with 4-PCO before incubation with 14,15[3H]EET enhanced A-23187-induced release of radiolabeled products into the medium. In contrast, 4-PCO did not alter uptake, distribution, or release of [3H]arachidonic acid. In porcine coronary arteries, 4-PCO augmented 14,15- EET-induced potentiation of endothelium-dependent relaxation to bradykinin. These data suggest that epoxide hydrolases may play a role in regulating EET incorporation into phospholipids, thereby modulating endothelial function in the coronary vasculature.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number5 46-5
StatePublished - Nov 1999
Externally publishedYes

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Epoxide Hydrolases
Phospholipids
Acids
Endothelium
Coronary Vessels
Swine
Calcimycin
Bradykinin
Arachidonic Acid
Cytochrome P-450 Enzyme System
Endothelial Cells
Lipids
14,15-epoxy-5,8,11-eicosatrienoic acid

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Dihydroxyeicosatrienoic acids
  • Porcine coronary artery

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids. / Weintraub, Neal L.; Fang, Xiang; Kaduce, Terry L.; VanRollins, Mike; Chatterjee, Papri; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 277, No. 5 46-5, 11.1999.

Research output: Contribution to journalArticle

Weintraub, Neal L. ; Fang, Xiang ; Kaduce, Terry L. ; VanRollins, Mike ; Chatterjee, Papri ; Spector, Arthur A. / Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids. In: American Journal of Physiology - Heart and Circulatory Physiology. 1999 ; Vol. 277, No. 5 46-5.
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