We have demonstrated that the principal enzymatic source of superoxide from ECs in insulin resistance is the Nox2 isoform of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) (8, 9, 10, 11, 12), and inhibition of Nox2 using pharmacological or genetic approaches can reduce superoxide generation, improve vascular function, and, in the case of pharmacological Nox2 inhibition, slow the progression of atherosclerosis in mice with EC-specific insulin resistance (13). Here, FMO5 is linked to atherosclerosis.