14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells

Xiang Fang, Steven A. Moore, Lynn L. Stoll, Gretchen Rich, Terry L. Kaduce, Neal L. Weintraub, Arthur A. Spector

Research output: Contribution to journalArticle

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Abstract

14,15-Epoxyeicosatrienoic acid (EET), a cytochrome P-450 epoxygenase product of arachidonic acid (AA), reduced PGE2 formation by 40-75% in porcine aortic and murine brain microvascular smooth muscle cells. The inhibition was reversed 6-10 h after removal of 14,15-EET from the medium and was regioisomeric specific; 8,9-EET produced a smaller effect, whereas 11,12- and 5,6-EET were ineffective. Although the cells converted 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-DHET did not inhibit PGE2 formation, and the 14,15-EET-induced inhibition was potentiated by 4- phenylchalcone oxide, an epoxide hydrolase inhibitor. The inhibition occurred when substrate amounts of AA were used and was not accompanied by enhanced production of other PGs, suggesting an effect on PGH synthase; however, in murine cells, 14,15-EET did not reduce PGH synthase mRNA or protein. Moreover, the 14,15-EET-induced decrease in PGE2 production was overcome by increasing the concentration of AA, but not oleic acid (which is not a substrate for PGH synthase). These findings suggest that 14,15-EET competitively inhibits PGH synthase activity in vascular smooth muscle cells. The 14,15-EET-induced inhibition of PGE2 production resulted in potentiation of platelet-derived growth factor-induced smooth muscle cell proliferation, suggesting that the competitive inhibition of PGH synthase by 14,15-EET can affect growth responses in smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)H2113-H2121
Number of pages9
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume275
Issue number6
StatePublished - Dec 1998

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Vascular Smooth Muscle
Dinoprostone
Smooth Muscle Myocytes
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
14,15-epoxy-5,8,11-eicosatrienoic acid
Epoxide Hydrolases
Platelet-Derived Growth Factor
Oleic Acid
Cytochrome P-450 Enzyme System
Swine
Cell Proliferation
Messenger RNA
Brain

Keywords

  • Arachidonic acid
  • Cytochrome P-450 epoxygenase
  • Dihydroxyeicosatrienoic acid
  • Prostaglandin H synthase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Fang, X., Moore, S. A., Stoll, L. L., Rich, G., Kaduce, T. L., Weintraub, N. L., & Spector, A. A. (1998). 14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells. American Journal of Physiology - Heart and Circulatory Physiology, 275(6), H2113-H2121.

14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells. / Fang, Xiang; Moore, Steven A.; Stoll, Lynn L.; Rich, Gretchen; Kaduce, Terry L.; Weintraub, Neal L.; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 275, No. 6, 12.1998, p. H2113-H2121.

Research output: Contribution to journalArticle

Fang, X, Moore, SA, Stoll, LL, Rich, G, Kaduce, TL, Weintraub, NL & Spector, AA 1998, '14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells', American Journal of Physiology - Heart and Circulatory Physiology, vol. 275, no. 6, pp. H2113-H2121.
Fang, Xiang ; Moore, Steven A. ; Stoll, Lynn L. ; Rich, Gretchen ; Kaduce, Terry L. ; Weintraub, Neal L. ; Spector, Arthur A. / 14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 1998 ; Vol. 275, No. 6. pp. H2113-H2121.
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