Role of myeloperoxidase in inflammation and atherosclerosis (Review)

Abstract

Myeloperoxidase (MPO) belongs to the heme peroxidase family, which includes a set of enzymes with potent oxidoreductase activity. MPO is considered an important part of the innate immune system's microbicidal arm and is secreted by neutrophils and macrophages. Interestingly, this enzyme has been implicated in the pathogenesis of several diseases including atherosclerosis. MPO is ubiquitous in atherosclerotic lesions and contributes to the initiation and progression of the disease primarily by oxidizing low-density lipoprotein (LDL) particles. MPO is the only human enzyme with the ability to produce hypochlorous acid (HOCl) at physiological chloride concentrations and HOCl-LDL epitopes were shown to be present inside atheromatous lesions making it a physiologically relevant model for the oxidation of LDL. It has been shown that MPO modified LDL is not able to bind to the native LDL receptor and is recognized instead by scavenger receptors on both endothelial cells and macrophages, which can lead to endothelial dysfunction and foam cell formation, respectively; both of which are instrumental in the progression of the disease. Meanwhile, several studies have proposed MPO as a biomarker for cardiovascular diseases where high levels of this enzyme were linked to an increased risk of developing coronary artery disease. Overall, there is sufficient evidence supporting the value of MPO as a crucial player in health and disease. Thus, future research should be directed towards investigating the still unknown processes associated with this enzyme. This may assist in better understanding the pathophysiological role of MPO, as well in the development of therapeutic strategies for protecting against the deleterious effects of MPO in numerous pathologies such as atherosclerosis.