Myeloperoxidase: A Leukocyte-Derived Protagonist of Inflammation and Cardiovascular Disease

Significance: The heme-enzyme myeloperoxidase (MPO) is one of the major neutrophil bactericidal proteins and is stored in large amounts inside azurophilic granules of neutrophils. Upon cell activation, MPO is released and extracellular MPO has been detected in a wide range of acute and chronic inflammatory conditions. Recent Advances and Critical Issues: Apart from its role during infection, MPO has emerged as a critical modulator of inflammation throughout the last decade and is currently discussed in the initiation and propagation of cardiovascular diseases. MPO-derived oxidants (e.g., hypochlorous acid) interfere with various cell functions and contribute to tissue injury. Recent data also suggest that MPO itself exerts proinflammatory properties independent of its catalytic activity. Despite advances in unraveling the complex action of MPO and MPO-derived oxidants, further research is warranted to determine the precise nature and biological role of MPO in inflammation. Future Directions: The identification of MPO as a central player in inflammation renders this enzyme an attractive prognostic biomarker and a potential target for therapeutic interventions. A better understanding of the (patho-) physiology of MPO is essential for the development of successful treatment strategies in acute and chronic inflammatory diseases. Antioxid. Redox Signal. 18, 692-713.