Linoleic Acid-Induced Endothelial Cell Injury: Role of Membrane-Bound Enzyme Activities and Lipid Oxidation

J Biochem Toxicol. Spring 1991;6(1):29-35. doi: 10.1002/jbt.2570060105.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Transporting ATPases / metabolism
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Deoxyribose / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology
  • Linoleic Acid
  • Linoleic Acids / toxicity*
  • Lipid Metabolism
  • Oxidation-Reduction
  • Peroxides / metabolism
  • Serum Albumin, Bovine / metabolism
  • Swine
  • Thiobarbiturates / metabolism
  • Time Factors


  • Linoleic Acids
  • Peroxides
  • Thiobarbiturates
  • Serum Albumin, Bovine
  • Deoxyribose
  • Linoleic Acid
  • Calcium-Transporting ATPases