Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque

Abstract

Our data implicate MPO in atherosclerotic plaque instability and suggest that non-invasive imaging and pharmacological inhibition of plaque MPO activity hold promise for clinical translation in the management of high-risk coronary artery disease.

An activatable PET imaging radioprobe is a dynamic reporter of myeloperoxidase activity in vivo

“…In atherosclerosis, MPO is overexpressed by activated macrophages and macrophage-derived foam cells (44,45) and is found in vulnerable plaques that may rupture (11). We and others have found that MPO imaging can identify highly inflamed plaques (46) and track treatment effects (47) in atherosclerotic plaques in rabbit and mouse models. We have also demonstrated the utility of 18 F-MAPP in MI imaging in this study.…”

The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease

“…The presence of MPO in the subendothelium has been implicated in plaque destabilization and thrombogenesis (200,247) as HOCl promotes endothelial cell apoptosis (141,273) and the release of tissue factor at sublethal oxidant doses (240). HOCl and MPO-H 2 O 2 -Cldirectly damage extracellular matrix components such as fibronectin, laminins, perlecan, and basement membrane materials, both in vitro and in vivo, with this having adverse effects on associated endothelial and smooth muscle cell function, viability, and gene expression (175,208).…”

“…Studies in a murine model of peritoneal inflammation have shown that 2-thioxanthine is an effective inhibitor and decreases HOCl production in vivo (253). More recently, AZM198, a thioxanthine derivative developed by AstraZeneca, inhibits MPO activity in a tandem stenosis model of atherosclerotic plaque instability in apolipoprotein E knockout (ApoE -/-) mice (200). This results in an increase in the fibrous cap thickness in unstable plaques and highlights the potential utility of MPO inhibition as a clinical strategy to improve outcomes in high-risk coronary artery disease patients (200).…”

eNOS-Nitric Oxide System Contributes to a Novel Antiatherogenic Effect of Leonurine via Inflammation Inhibition and Plaque Stabilization

“…This animal model has been widely used ever since due to its strength at mimicking pathological changes in life-threatening clinical cardiovascular events. (Rashid et al, 2018) Metabolic disturbance not only induces endothelial cell dysfunction at the onset stage of atherosclerosis, but also weakens endothelial barrier in advanced atherosclerotic plaques.…”