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20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells. J Biol Chem 2004 Jan 23;279(4):2648-56 PMID: 14612451

Pubmed ID

14612451

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 omega-oxidases. Porcine coronary artery endothelial cells (PCEC) incorporated 20-[(3)H]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-[(3)H]HETE increased substantially when methyl arachidonoyl fluorophosphonate, but not bromoenol lactone, was added, suggesting that a Ca(2+)-dependent cytosolic phospholipase A(2) released the 20-HETE contained in PCEC phospholipids. Addition of calcium ionophore A23187 produced a rapid release of 20-[(3)H]HETE from the PCEC, a finding that also is consistent with a Ca(2+)-dependent mobilization process. PCEC also converted 20-[(3)H]HETE to 20-carboxy-arachidonic acid (20-COOH-AA) and 18-, 16-, and 14-carbon beta-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.

Author List

Kaduce TL, Fang X, Harmon SD, Oltman CL, Dellsperger KC, Teesch LM, Gopal VR, Falck JR, Campbell WB, Weintraub NL, Spector AA

Author

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-9144262957   43 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Biological Transport, Active
Calcimycin
Coronary Vessels
Endothelium, Vascular
Hydroxyeicosatetraenoic Acids
Ionophores
Swine
Time Factors
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e