Coupling eNOS Uncoupling to the Innate Immune Response

The endothelial isoform of nitric oxide synthase(eNOS) has been well recognized for its central role inconserving vascular homeostasis by inducing quies-cence of endothelial cells and adjacent vessel wall structures. For example, eNOS-derived NO can alter protein function by S-nitrosylation of cysteine residues and, in endothelial cells, patterns of S-nitrosylated transcriptional regulators have been shown to interrupt inflammatory signaling and induce cell cycle arrest.1 Likewise, by competing with oxygen as an electron acceptor at complex IV, NO can limit energy expenditure through reducing oxidative phosphorylation dur-ing episodes of hypoxic challenge.2 See page 2688 Yet eNOS has also been recognized as a source of non-nitrous reactive oxygen species that can elicit a coordinated proin-flammatory response. This is related to the basic chemistry in the enzyme where NADPH-derived electrons flow from the