HETEs and coronary artery endothelial cells: metabolic and functional interactions

Porcine coronary artery endothelial cells have been established in culture. These cells produce prostaglandin (PG) I2, PGF2 alpha, and PGE2 when exposed to either arachidonic acid or ionophore A23187. PG formation was reduced when the cells were exposed to monohydroxy and dihydroxy unsaturated fatty acids. Although all of the hydroxyeicosatetraenoic acids (HETEs) produced reductions, 5-HETE caused the largest decrease in PGI2 formation. Therefore, these lipoxygenase products, especially 5-HETE, may impair the nonthrombogenic surface and some vasodilator responses of coronary endothelium. The cells took up each of the HETEs and incorporated them into phospholipids. Uptake was not affected by equimolar amounts of oleic or linoleic acids; even arachidonic acid reduced 12- and 15-HETE uptake by only 50-60%. Like other cells, the coronary endothelium converted 12- and 15-HETE to polar metabolites. As opposed to other cells, however, these cultures also converted 5-HETE to a more polar metabolite. Thus coronary artery endothelium can take up and metabolize all of the major HETEs, including 5-HETE, and thereby reduce their potentially injurious effects in the coronary circulation.