Intraplaque Myeloperoxidase Activity as Biomarker of Unstable Atheroma and Adverse Clinical Outcomes in Human Atherosclerosis.

ABSTRACT

Background: The detection of unstable atherosclerosis remains elusive. Intraplaque myeloperoxidase (MPO) activity causes plaque destabilization in preclinical models, holding promise for clinical translation as a novel imaging biomarker. Objectives: The purpose of this study was to assess whether MPO activity is greater in unstable human plaques, how this relates to cardiovascular events and current/emerging non-invasive imaging techniques. Methods: Thirty-one carotid endarterectomy specimens and 12 coronary trees were collected. MPO activity was determined in 88 individual samples through the conversion of hydroethidine to the MPO-specific adduct 2-chloroethidium and compared with macroscopic validation, histology, clinical outcomes, and computed tomography-derived high and low attenuation plaques and perivascular adipose tissue. Non-parametric statistical analysis utilizing Mann-Whitney U and Kruskal-Wallis tests for univariate and group comparisons were performed. Results: Unstable compared with stable plaque had higher MPO activity (carotid endarterectomy n = 26, 4.2 ± 3.1 vs 0.2 ± 0.3 nmol/mgp; P < 0.0001; coronary n = 17, 0.6 ± 0.5 vs 0.001 ± 0.003 nmol/mgp; P = 0.0006). Asymptomatic, stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke (n = 12, 3.7 ± 2.1 vs 0.1 ± 0.2 nmol/mgp; P = 0.002). Computed tomography-determined plaque attenuation did not differentiate MPO activity (n = 30, 0.1 ± 0.1 vs 0.2 ± 0.3 nmol/mgp; P = 0.23) and MPO activity was not found in perivascular adipose tissue. Conclusions: MPO is active within unstable human plaques and correlates with symptomatic carotid disease and stroke, yet current imaging parameters do not identify plaques with active MPO. As intraplaque MPO activity can be imaged non-invasively through novel molecular imaging probes, ongoing investigations into its utility as a diagnostic tool for high-risk atherosclerosis is warranted.