Selenium inhibits 15-hydroperoxyoctadecadienoic acid-induced intracellular adhesion molecule expression in aortic endothelial cells

Increased intracellular adhesion molecule 1 (ICAM-1) expression and enhanced monocyte recruitment to the endothelium are critical steps in the early development of atherosclerosis. The 15-lipoxygenase 1 (15-LOX1) pathway can generate several proinflammatory eicosanoids that are known to enhance ICAM-1 expression within the vascular endothelium. Oxidative stress can exacerbate endothelial cell inflammatory responses by modifying arachidonic acid metabolism through the 15-LOX1 pathway. Because selenium (Se) influences the oxidant status of cells and can modify the expression of eicosanoids, we investigated the role of this micronutrient in modifying ICAM-1 expression as a consequence of enhanced 15-LOX1 activity. Se supplementation reduced ICAM-1 expression in bovine aortic endothelial cells, an effect that was reversed with 15-LOX1 overexpression or treatment with exogenous 15-hydroperoxyoctadecadienoic acid (15-HPETE). ICAM-1 expression increased proportionately when intracellular 15-HPETE levels were allowed to accumulate. However, changes in intracellular 15-HETE levels did not seem to affect ICANI-1 expression regardless of Se status. Our results indicate that Se supplementation can reduce 15-HPETE-induced expression of ICAM-I by controlling the intracellular accumulation of this fatty acid hydroperoxide in endothelial cells. (C) 2007 Elsevier Inc. All rights reserved.