Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide

Xiang Fang, Neal Lee Weintraub, Christine L. Oltman, Lynn L. Stoll, Terry L. Kaduce, Shawn Harmon, Kevin C Dellsperger, Christophe Morisseau, Bruce D. Hammock, Arthur A. Spector

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of vascular reactivity and function. Conversion to the corresponding dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolases is thought to be the major pathway of EET metabolism in mammalian vascular cells. However, when human coronary artery endothelial cells (HCEC) were incubated with 3 H-labeled 14,15-EET, chain-shortened epoxy fatty acids, rather than DHET, were the most abundant metabolites. After 4 h of incubation, 23% of the total radioactivity remaining in the medium was converted to 10,11-epoxy-hexadecadienoic acid (16:2), a product formed from 14,15-EET by two cycles of β-oxidation, whereas only 15% was present as 14,15-DHET. Although abundantly present in the medium, 10,11-epoxy-16:2 was not detected in the cell lipids. Exogenously applied 3 H-labeled 10,11-epoxy-16:2 was neither metabolized nor retained in the cells, suggesting that 10,11-epoxy-16:2 is a major product of 14,15-EET metabolism in HCEC. 10,11-Epoxy-16:2 produced potent dilation in coronary microvessels. 10,11-Epoxy-16:2 also potently inhibited tumor necrosis factor-α-induced production of IL-8, a proinflammatory cytokine, by HCEC. These findings implicate β-oxidation as a major pathway of 14,15-EET metabolism in HCEC and provide the first evidence that EET-derived chain-shortened epoxy fatty acids are biologically active.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
StatePublished - Dec 1 2002

Fingerprint

Epoxy Compounds
Coronary Vessels
Endothelial Cells
Blood Vessels
Fatty Acids
Epoxide Hydrolases
Acids
Microvessels
Interleukin-8
Cytochrome P-450 Enzyme System
Radioactivity
Dilatation
Tumor Necrosis Factor-alpha
Cytokines
Lipids
14,15-epoxy-5,8,11-eicosatrienoic acid

Keywords

  • Beta-oxidation
  • Epoxyeicosatrienoic acid
  • Inflammation
  • Vasorelaxation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide. / Fang, Xiang; Weintraub, Neal Lee; Oltman, Christine L.; Stoll, Lynn L.; Kaduce, Terry L.; Harmon, Shawn; Dellsperger, Kevin C; Morisseau, Christophe; Hammock, Bruce D.; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 6 52-6, 01.12.2002.

Research output: Contribution to journalArticle

Fang, X, Weintraub, NL, Oltman, CL, Stoll, LL, Kaduce, TL, Harmon, S, Dellsperger, KC, Morisseau, C, Hammock, BD & Spector, AA 2002, 'Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide', American Journal of Physiology - Heart and Circulatory Physiology, vol. 283, no. 6 52-6.
Fang, Xiang ; Weintraub, Neal Lee ; Oltman, Christine L. ; Stoll, Lynn L. ; Kaduce, Terry L. ; Harmon, Shawn ; Dellsperger, Kevin C ; Morisseau, Christophe ; Hammock, Bruce D. ; Spector, Arthur A. / Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 283, No. 6 52-6.
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abstract = "Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of vascular reactivity and function. Conversion to the corresponding dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolases is thought to be the major pathway of EET metabolism in mammalian vascular cells. However, when human coronary artery endothelial cells (HCEC) were incubated with 3 H-labeled 14,15-EET, chain-shortened epoxy fatty acids, rather than DHET, were the most abundant metabolites. After 4 h of incubation, 23{\%} of the total radioactivity remaining in the medium was converted to 10,11-epoxy-hexadecadienoic acid (16:2), a product formed from 14,15-EET by two cycles of β-oxidation, whereas only 15{\%} was present as 14,15-DHET. Although abundantly present in the medium, 10,11-epoxy-16:2 was not detected in the cell lipids. Exogenously applied 3 H-labeled 10,11-epoxy-16:2 was neither metabolized nor retained in the cells, suggesting that 10,11-epoxy-16:2 is a major product of 14,15-EET metabolism in HCEC. 10,11-Epoxy-16:2 produced potent dilation in coronary microvessels. 10,11-Epoxy-16:2 also potently inhibited tumor necrosis factor-α-induced production of IL-8, a proinflammatory cytokine, by HCEC. These findings implicate β-oxidation as a major pathway of 14,15-EET metabolism in HCEC and provide the first evidence that EET-derived chain-shortened epoxy fatty acids are biologically active.",
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AU - Weintraub, Neal Lee

AU - Oltman, Christine L.

AU - Stoll, Lynn L.

AU - Kaduce, Terry L.

AU - Harmon, Shawn

AU - Dellsperger, Kevin C

AU - Morisseau, Christophe

AU - Hammock, Bruce D.

AU - Spector, Arthur A.

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