Myeloperoxidase, modified lipoproteins, and atherogenesis

Abstract

Numerous lines of evidence implicate a role for myeloperoxidase (MPO) in the pathogenesis of atherosclerosis. Enriched within vulnerable plaque, MPO serves as an enzymatic source of eicosanoids and bioactive lipids and generates atherogenic forms of both low- and high-density lipoproteins. These factors likely contribute to clinical studies demonstrating that increased systemic levels of MPO and its oxidation products predict increased cardiovascular risk. As a result, interest has focused on the potential to target MPO for the development of new risk markers, imaging, and therapies to prevent cardiovascular events.

Fig. 1.

Role of MPO-catalyzed pathways in the generation of atherogenic LDL and dysfunctional HDL particles. MPO-generated products promote lipid peroxidation, conversion of LDL to a high-uptake form, and impairment of the ability of apoA-I to promote cholesterol efflux. MPO-catalyzed carbamylation has recently been reported also to be involved in generation of high-uptake forms of LDL and impaired functional activities of HDL.