Abstract 9588: Intraplaque Myeloperoxidase Activity is a Hallmark of Vulnerable Atherosclerosis and Correlates With Clinical Outcomes

Abstract

Introduction: There remains limited means by which to detect unstable atherosclerosis in patients at risk of myocardial infarction and stroke. Myeloperoxidase (MPO) is increased in unstable plaque and causally linked to plaque destabilization and rupture in pre-clinical models. We sought to assess whether MPO activity is greater in vulnerable human carotid and coronary atheroma, and how this relates to adverse cardiovascular events and non-invasive imaging parameters. Methods: Carotid endarterectomy specimens (CEA) were collected from 31 patients. Coronary trees were collected from 12 patients undergoing heart transplantation for ischemic cardiomyopathy. MPO activity was assessed through the conversion of hydroethidine added to tissue sections to the MPO-specific adduct 2-chloroethidium (2-Cl-E + ) and quantified by mass spectrometry. MPO activity was then compared with histologic determination of plaque phenotype and clinical outcomes. MPO activity was additionally assessed in high and low attenuation plaques derived by computed tomography, as well as perivascular adipose tissue (PVAT). Results: Unstable CEA had higher MPO activity when compared with stable CEA plaques (n = 26, 4.2 ± 3.1 vs. 0.2 ± 0.3 μmol/mgp; p < 0.0001). Similar results were seen in coronary segments with unstable compared to stable plaque (n = 17, 0.6 ± 0.5 vs. 0.0 ± 0.0 μmol/mgp; p = 0.0006). When comparing MPO activity in CEA to clinical outcomes, asymptomatic and stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke on neuroimaging (n = 12, 3.7 ± 2.1 vs. 0.1 ± 0.2 μmol/mgp; p = 0.002). CT-determined plaque attenuation did not identify plaque MPO activity (n = 30, 0.1 ± 0.1 vs. 0.2 ± 0.3 μmol/mgp; p = 0.23) and enzymatically active MPO was not found in PVAT. Conclusion: MPO is active within unstable human carotid and coronary plaques and correlates with symptomatic carotid disease and stroke. In addition, current non-invasive imaging parameters do not selectively identify plaques enriched with active MPO. As intraplaque MPO appears to be a hallmark of unstable atherosclerosis and can potentially be imaged non-invasively, further investigation into its potential utility as a diagnostic tool for high-risk atherosclerosis is warranted.