The Resurrection of Myeloperoxidase as a Therapeutic Target

SEE PAGE 633 T he innate immune response is critical to our survival as human beings. An important component of the innate immune response is the release of myeloperoxidase (MPO) predominantly from neutrophils upon activation. MPO generates numerous reactive oxidant species and has the unique ability to produce reactive chlorinating species which are particularly potent against invading viruses and bacteria (1). However, innate immunity can also be involved in causing disease and has been shown to play a critical role in the pathogenesis of coronary artery disease (CAD), myocardial infarction (MI), and heart failure (2). While some immune effects may be similarly beneficial in CAD, the majority of immune contributions, and particularly those of neutrophil-derived MPO, seems to wreak inflammatory havoc culminating in atherosclerosis progression, plaque instability, acute coronary syndromes, and adverse ventricular remodeling following MI (3). MPO seems like an obvious target for CAD and heart failure therapies. As early as the 1960s, the key role of MPO in the innate immune response was gaining interest (4). The realization that MPO and its products were expressed in human atherosclerotic plaque, first noted in the 1990s, sparked intense interest in its possible contribution to CAD (5). Further studies demonstrated that the inflammatory cell infiltrate, driven in large part by the release of MPO from neutrophils, is a key contributor to creating the milieu for plaque development and myocardial injury