Myeloperoxidase Interactions with Nitric Oxide: A Review of Mechanistic Pathways

Abstract

The phagocytic enzyme myeloperoxidase (MPO) plays an essential role in the inflammatory response by catalyzing formation of reactive species involved in microbial killing by generating hypochlorous acid (HOCl) from H2O2 and physiological (≥100 mM) Cl⁻ concentrations. However, increased MPO activity has been linked to a number of pathologies with compelling evidence in initiation and progression of inflammatory events. For example, leukocyte and serum MPO levels are elevated in patients with coronary artery disease and thus may be used as a marker for cardiovascular events. MPO-derived oxidants have been linked with neurodegenerative disorders, carcinogenesis, lung disease and respiratory damage, rheumatoid arthritis, kidney damage and atherosclerosis, respectively. Recent data showed the link between increase levels of MPO and development of diabetes, implicating the enzyme as a catalyst for oxidative reactions in the vascular wall. One of the important molecules directly modulated by MPO is nitric oxide, whose bioavailability plays the central role in the development of different pathophysiologies. Thus, we reviewed and analyzed available data and proposed the comprehensive reaction pathways connecting inflammatory action of MPO and bioavailability of NO resulting in a major disturbance of normal physiological functions.