Interactions Between Nitric Oxide and Lipid Oxidation Pathways

Abstract

—Nitric oxide (^·NO) signaling pathways and lipid oxidation reactions are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Because both of these pathways involve free radical species that can also react together at extremely fast rates, convergent interactions between these pathways are expected. Biochemical and cell biology studies have defined multiple interactions of ^·NO with oxidizing lipids that could lead to either vascular protection or potentiation of inflammatory vascular injury. For example, low levels of ^·NO generated by endothelial nitric oxide synthase can terminate propagating lipid radicals and inhibit lipoxygenases, reactions that would be protective. Alternatively, if generated at elevated levels, for example, after inducible nitric oxide synthase expression in inflammation, ^·NO can be converted to prooxidant species, such as peroxynitrite (ONOO^–) and nitrogen dioxide (^·NO₂), that can potentiate inflammatory injury to vascular cells. Finally, both enzymatic and nonenzymatic lipid oxidation reactions can influence ^·NO bioactivity by directly scavenging ^·NO or altering the induction and catalytic activity of nitric oxide synthase enzymes. In this review, we summarize the biochemical interactions between ^·NO and lipid oxidation reactions and discuss the recognized and potential roles of these reactions in the vasculature.