Fatty acid supplementation protects pulmonary artery endothelial cells from oxidant injury

Although supplemental fatty acids have been shown to alter the susceptibility of experimental animals to oxidant gases, the relationship between the degree of tissue fatty acyl unsaturation and resistance to oxidant exposure remains undefined. Because vascular endothelial cells have been demonstrated to be sensitive cellular targets in oxidant-induced lung injury, we evaluated the effects of a supplemental fatty acid on the lipid composition and oxidant susceptibility of pulmonary artery endothelial cells (PAEC) in monolayer culture. PAEC were incubated in culture medium supplemented with an ethanolic solution of 0.1 mM cis-vaccenic acid (CVA), an 18-carbon monounsaturated fatty acid, or with the ethanol vehicle alone for 3 h. Cells were then exposed to either control or oxidant (hyperoxia: 95% O2; or hydrogen peroxide: 100 microM) conditions. Oxidant-induced cell injury was assessed by phase-contrast microscopy and by measuring the release of intracellular lactate dehydrogenase. Incubation with CVA increased the CVA content of PAEC lipids and protected cells from oxidant-induced injury for up to 72 h after supplementation. CVA had no effect on nonoxidant-induced cell injury. Although the mechanism by which CVA protects cells against oxidant injury remains undefined, evidence is presented that indicates the mechanism does not involve induction of antioxidant enzyme activity, alterations in the physical state of PAEC membranes, or enhancement of PAEC nucleic acid repair mechanisms. These results define a useful model for exploring the relationship between lipid composition and oxidant susceptibility and suggest that fatty acid modifications may constitute an important strategy for protecting cells against oxidant injury.