Nitrated lipids: defining their bioactivity.

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Nitric oxide (NO) is an endogenously generated diffusible messenger that mediates a multitude of physiological and pathological processes. Normally, NO is produced in low concentrations and acts both as a messenger and cytoprotective factor via direct interactions with transition metals and other free radicals. However, in the setting of inflammation or shock, the substantial amounts of NO released may lead to the formation of cytotoxic species. When NO is transformed into a nitrating or nitrosating species it can readily react with many other factors potentially modulating their biological activity. These NO-dependent interactions are central in the regulation of many processes affecting vascular and atherothrombotic disease. Previous studies have shown that NO reacts with both lipids and lipoproteins. The interaction of NO with oxidizing lipids can be either protective to the vasculature or enhance inflammatory-mediated vascular injury. In certain situations, low levels of NO generated by endothelial NO synthase (eNOS) can terminate lipid radical chain propagation reactions.1 Conversely, prooxidant reactions can occur after superoxide reacts with NO and leads to the formation of potent secondary oxidants, such as peroxynitrite and nitrogen dioxide, that can enhance inflammatory injury to vascular cells.2 Unsaturated lipids of membranes and lipoproteins can be critical targets of reactive oxygen and nitrogen species, suggesting potential relevance for nitrogen-containing lipid products. When NO is transformed into a nitrating and nitrosating species, it has been shown to react with unsaturated lipids.3,4⇓ Recently, such nitrated lipids have been demonstrated to be formed in vivo.5 The oxidation product of NO, NO2, has been shown to react with arachidonic acid generating …