20-Hydroxyeicosatetraenoic Acid (20-HETE) Metabolism in Coronary Endothelial Cells

Terry L. Kaduce, Xiang Fang, Shawn D. Harmon, Christine L. Oltman, Kevin C. Dellsperger, Lynn M. Teesch, V. Raj Gopal, J. R. Falck, William B. Campbell, Neal L. Weintraub, Arthur A. Spector

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

We have investigated the role of endothelial cells in the metabolism of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive mediator synthesized from arachidonic acid by cytochrome P450 ω-oxidases. Porcine coronary artery endothelial cells (PCEC) incorporated 20-[3H]HETE primarily into the sn-2 position of phospholipids through a coenzyme A-dependent process. The incorporation was reduced by equimolar amounts of arachidonic, eicosapentaenoic or 8,9-epoxyeicosatrienoic acids, but some uptake persisted even when a 10-fold excess of arachidonic acid was available. The retention of 20-[3H]HETE increased substantially when methyl arachidonoyl fluorophosphonate, but not bromoenol lactone, was added, suggesting that a Ca2+-dependent cytosolic phospholipase A2 released the 20-HETE contained in PCEC phospholipids. Addition of calcium ionophore A23187 produced a rapid release of 20-[3H]HETE from the PCEC, a finding that also is consistent with a Ca2+-dependent mobilization process. PCEC also converted 20-[3H]HETE to 20-carboxy-arachidonic acid (20-COOH-AA) and 18-, 16-, and 14-carbon β-oxidation products. 20-COOH-AA produced vasodilation in porcine coronary arterioles, but 20-HETE was inactive. These results suggest that the incorporation of 20-HETE and its subsequent conversion to 20-COOH-AA in the endothelium may be important in modulating coronary vascular function.

Original languageEnglish (US)
Pages (from-to)2648-2656
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number4
DOIs
StatePublished - Jan 23 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kaduce, T. L., Fang, X., Harmon, S. D., Oltman, C. L., Dellsperger, K. C., Teesch, L. M., Gopal, V. R., Falck, J. R., Campbell, W. B., Weintraub, N. L., & Spector, A. A. (2004). 20-Hydroxyeicosatetraenoic Acid (20-HETE) Metabolism in Coronary Endothelial Cells. Journal of Biological Chemistry, 279(4), 2648-2656. https://doi.org/10.1074/jbc.M306849200