LINOLEIC ACID-INDUCED ENDOTHELIAL-CELL INJURY - ROLE OF MEMBRANE-BOUND ENZYME-ACTIVITIES AND LIPID OXIDATION

High plasma levels of linoleic acid (18:2) may injure endothelial cells, resulting in decreased barrier function of the vascular endothelium. The effects of linoleic acid on endothelial barrier function (transendothelial movement of albumin), membrane-bound enzyme activities, and possible autooxidation of linoleic acid under experimental conditions were studied. The exposure of endothelial monolayers to 18:2 for 24 hr at 60, 90, and 120-mu-M fatty acid concentrations caused a significant increase in transendothelial movement of albumin, with maximum albumin transfer at 90-mu-M. Fatty acid treatment resulted in the increased appearance of cytosolic lipid droplets. Activities of the membrane-bound enzymes, angiotensin-converting enzyme (ACE), and Ca2+-ATPase increased steadily with increasing time of cell exposure to 90-mu-M 18:2, reaching significance at 24 hr. Treatment of endothelial cultures with up to 120-mu-M 18:2 did not cause cytotoxicity, as evidenced by a nonsignificant change in cellular release of [H-3]-adenine. Incubation of 18:2-supplemented serum-containing culture media with 1000-mu-M 18:2 at 37-degrees-C for up to 48 hr did not result in formation of autooxidation products. These results suggest that 18:2 itself, and not its oxidation products, plays a major role in disrupting endothelial barrier function.