Fig. 8. Proposed model for the mechanism of linoleic acid (LA)-mediated endothelial cell activation. LA treatment results in CYP 2C9 activation and production of superoxide radicals as well as depletion of glutathione in endothelial cells. The increased oxidative stress results in the activation of oxidative stress sensitive transcription factors such as NF-B and AP-1, leading to endothelial cell activation. Sulfaphenazole, a specific inhibitor of CYP 2C9 suppresses the oxidative stress caused by LA treatment. The formation of leukotoxin and leukotoxin diol under physiological condition may help in the fatty acid detoxification process.