Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease

► Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) is an anti-atherosclerotic molecule. ► Hypercholesterolemia leads to oxidative stress, uncoupling of eNOS and reduced eNOS activity. ► The resulting reduction in NO bioavailability promotes atherogenesis. ► Some compounds can prevent eNOS uncoupling and enhance eNOS activity at the same time. ► Such pharmacological approaches are of therapeutic interest.