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 microM fatty acid concentrations caused a significant increase in transendothelial movement of albumin, with maximum albumin transfer at 90 microM. Fatty acid treatment resulted in the increased appearance of cytosolic lipid droplets. Activities of the membrane-bound enzymes, angiotensin-converting enzyme (ACE), and Ca(2+)-ATPase increased steadily with increasing time of cell exposure to 90 microM 18:2, reaching significance at 24 hr. Treatment of endothelial cultures with up to 120 microM 18:2 did not cause cytotoxicity, as evidenced by a nonsignificant change in cellular release of [3H]-adenine. Incubation of 18:2-supplemented serum-containing culture media with 1000 microM 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.
Ramasamy
S
S
Department of Nutrition, University of Kentucky, Lexington 40506.
Boissonneault
G A
GA
Decker
E A
EA
Hennig
B
B
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003855:Deoxyribose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000633:toxicity*; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013552:Swine; D013858:Thiobarbiturates / Q000378:metabolism; D013997:Time Factors
D008041:Linoleic Acids; D010545:Peroxides; D013858:Thiobarbiturates; D012710:Serum Albumin, Bovine; D003855:Deoxyribose; D019787:Linoleic Acid; D000252:Calcium-Transporting ATPases