Endothelial nitric oxide synthase: host defense enzyme of the endothelium?

This article explores the physiology of superoxide generation by endothelial nitric oxide synthase (eNOS), the so-called "uncoupled" state of the enzyme. The fact that this alternative chemistry of the eNOS enzyme is evolutionary strongly conserved, suggests that it may play a physiological role. It is proposed that this uncoupled state may contribute to defense against infections. As the switch from NO production to reactive oxygen species by eNOS is also the final common pathway in atherogenesis, the uncoupling of eNOS further builds on the hypothesis that atherogenesis is driven by cellular mechanisms that originally serve host defense. The central role of uncoupled eNOS in redox signaling in the endothelium may open up new avenues for therapy to prevent atherosclerosis.