Myeloperoxidase – A bridge linking inflammation and oxidative stress with cardiovascular disease

Myeloperoxidase (MPO) is a member of the superfamily of heme peroxidases that is mainly expressed in neutrophils and monocytes. MPO-derived reactive species play a key role in neutrophil antimicrobial activity and human defense against various pathogens primarily by participating in phagocytosis. Elevated MPO levels in circulation are associated with inflammation and increased oxidative stress. Multiple lines of evidence suggest an association between MPO and cardiovascular disease (CVD) including coronary artery disease, congestive heart failure, arterial hypertension, pulmonary arterial hypertension, peripheral arterial disease, myocardial ischemia/reperfusion-related injury, stroke, cardiac arrhythmia and venous thrombosis. Elevated MPO levels are associated with a poor prognosis including increased risk for overall and CVD-related mortality. Elevated MPO may signify an increased risk for CVD for at least 2 reasons. First, low-grade inflammation and increased oxidative stress coexist with many metabolic abnormalities and comorbidities and consequently an elevated MPO level may represent an increased cardiometabolic risk in general. Second, MPO produces a large number of highly reactive species which can attack, destroy or modify the function of every known cellular component. The most common MPO actions relevant to CVD are generation of dysfunctional lipoproteins with an increased atherogenicity potential, reduced NO availability, endothelial dysfunction, impaired vasoreactivity and atherosclerotic plaque instability. These actions strongly suggest that MPO is directly involved in the pathophysiology of CVD. In this regard MPO may be seen as a mediator or an instrument through which inflammation promotes CVD at molecular and cellular level. Clinical value of MPO therapeutic inhibition remains to be tested.