Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification?
Roger K. Schindhelm, Leonard P. van der Zwan, Tom Teerlink and Peter G. Scheffer



BACKGROUND: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
CONTENT: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation betweenMPOand CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linkingMPOto accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
SUMMARY: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improveCVDrisk estimation. BeforeMPOcan be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed.


Figure 1. Adverse effects of MPO in the vasculature.

LDL particles penetrating the arterial intima may be minimally modified (mmLDL) by reactive oxygen species (ROS). Subsequently, mmLDL induces monocytes to migrate into the vascular wall, where they differentiate into macrophages. Oxidized LDL (oxLDL) is recognized by scavenger receptors of macrophages, and excess uptake leads to foam cell formation. MPO is released by macrophages in a state of inflammation and catalyzes the formation of myeloperoxidase-derived reactive species (MDRS) using chloride, thiocyanate, or NO as substrate and hydrogen peroxide as cosubstrate. Scavenging of NO may result in impaired vasodilation. Moreover, MDRS may promote atherosclerosis in different ways as indicated by the blue arrows. MDRS may oxidize LDL particles more extensively, forming oxidized LDL (oxLDL), and render HDL dysfunctional by promoting formation of oxidized HDL (oxHDL), thereby impairing HDL’s protective effect on LDL particles and inhibiting reverse-cholesterol transport. MDRS may also destabilize plaques by weakening the fibrous cap.

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