Effect of fatty acid modification on prostacyclin production by cultured human endothelial cells

We have investigated whether changes in cellular fatty acid saturation can influence prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells. As compared to control cells, those enriched with linoleic acid released 60--75% less PGI2 in response to thrombin or the calcium ionophore A23187. A similar but considerably smaller effect was observed when the cells were enriched with oleic or linolenic acid, but no reduction occurred with palmitic or linoelaidic acids. Some reduction in PGI2 release was noted as early as 1 h after exposure to linoleic acid. When the culture medium was supplemented with linoleic acid, the cell phospholipids contained four to five times more linoleate and 25--40% less arachidonate. These changes were most marked in the choline and serine plus inositol phosphoglyceride fractions. When the fatty acid composition of the cells enriched with linoleic acid was allowed to revert, there was a progressive increase in the capacity of the cells to release PGI2 in response to thrombin. The increase correlated with a reduction in linoleate content of the cell lipids, but there was no change in arachidonate content. This suggests that linoleic acid may act as an inhibitor of PGI2 production. The cultured endothelial cells were also able to produce PGI2 directly from added arachidonic acid. As the arachidonic acid concentration of the medium was raised, PGI2 formation by the linoleate-enriched cells increased relative to control cells, suggesting that the inhibition produced by linoleic acid may be competitive.