Free radicals and lipid signaling in endothelial cells

Lipid mediators generated by oxidative pathways play essential roles in vascular homeostasis and disease through activating signal transduction pathways that control a variety of cellular functions, including vascular tone, gene expression, and leukocyte and platelet activation. Several enzyme families generate oxidized lipids, and a number of these are either constitutively expressed or inducible in the endothelium, including prostaglandin H synthases, lipoxygenases, and cytochrome P450 isoforms. Mediators generated by these enzymes are predominantly arachidonate-derived and include lipid hydroxides, epoxides, hydroperoxides, and prostanoids. These enzymes may also generate low levels of lipid-derived radicals in the vasculature following escape of substrate radicals from the active site. Lipid oxidation enzymes are often up-regulated in atherosclerosis and hypertension, with several lines of evidence suggesting that they play a central role in the pathogenesis of the disease process itself. This review will describe the isoforms of lipid oxidation enzymes present in endothelial cells focusing on their physiological functions and proposed roles in initiation and progression of vascular disease.