Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease

Abstract

ABSTRACTBackground: Monocytes and macrophages are central to atherosclerosis, but how they mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients’ monocyte subtypes paired with their derived macrophage profiles correlate with extent of CAD.Methods: Peripheral blood was collected from 30 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease, or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for polarization markers CD86 and CD206.Results: At baseline, patients with greater CAD burden were older with higher rates of statin use, whereas all other characteristics were similar across the spectrum of coronary disease. Non-classical (CD14loCD16hi) and all CD16+ monocytes were elevated in patients with single vessel and multivessel disease compared to those without significant CAD (8.6% and 10.5% vs. 2.8%, p < 0.05), whereas regulatory M2 macrophages (CD206+) were decreased in patients with single vessel and multivessel disease (0.34% and 0.34% vs. 1.4%, p < 0.05). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. CAD was also found to be more tightly associated with CD16+ cells than age or traditional cardiovascular risk factors on multiple regression analysis of these patients.Conclusions: CAD extent is correlated directly with CD16+ monocytes and inversely with M2 (CD206+) macrophages, suggesting circulating monocytes may influence downstream polarization of lesional macrophages. These measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.