Coupling eNOS uncoupling to the innate immune response.

The endothelial isoform of nitric oxide synthase (eNOS) has been well recognized for its central role in conserving vascular homeostasis by inducing quiescence 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 during episodes of hypoxic challenge.2