Eicosapentaenoic acid and prostacyclin production by cultured human endothelial cells.
Human umbilical vein endothelial cells incorporate eicosapentaenoic acid (EPA) when this fatty acid is present in the culture medium. From 30 to 70% of the uptake remains as EPA, and much of the remainder is elongated to docosapentaenoic acid. All of the cellular glycerophospholipids become enriched with EPA and docosapentaenoic acid, with the largest increase in EPA occurring in the choline glycerophospholipids. When this fraction is enriched with EPA, it exhibits a large decrease in arachidonic acid content. Cultures exposed to tracer amounts of [1-14C]linolenic acid in 5% fetal bovine serum convert as much as 17% of the radioactivity to EPA. The conversion is reduced, however, in the presence of either 20% fetal bovine serum or 50 microM linolenic acid. Like arachidonic acid, some newly incorporated EPA was released from the endothelial cells when the cultures were exposed to thrombin. However, as compared with arachidonic acid, only very small amounts of EPA were converted to prostaglandins. Cultures enriched with EPA exhibited a 50 to 90% reduction in capacity to release prostacyclin (PGI2) when subsequently stimulated with thrombin, calcium ionophore A23187, or arachidonic acid. The degree of inhibition was dependent on the time of exposure to EPA and the EPA concentration, and it was not prevented by adding a reversible cyclooxygenase inhibitor, ibuprofen, during EPA supplementation. EPA appears to decrease the capacity of the endothelial cells to produce PGI2 in two ways: by reducing the arachidonic acid content of the cell phospholipid precursor pools and by acting as an inhibitor of prostaglandin production. These findings suggest that regimens designed to reduce platelet aggregation and thrombosis by EPA enrichment may also reduce the capacity of the endothelium to produce PGI2.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011247:Pregnancy; D013917:Thrombin / Q000502:physiology; D014471:Umbilical Veins / Q000378:metabolism*
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol; D013917:Thrombin