Monocyte and macrophage subtypes as paired cell biomarkers for coronary artery disease

Abstract

New Findings What is the central question of this study?Are circulating monocyte markers correlated with their derived macrophage polarization patterns and coronary artery disease severity? What is the main finding and its importance?There was an inverse relationship between circulating CD16+ monocytes (high) and M2 macrophages (low) that marked coronary disease severity, and the differences in polarization of macrophages were seen despite a week of cell culture ex vivo. This study highlights the importance, and potential prognostic implications, of circulating monocyte and descendant macrophage phenotypes in coronary artery disease. Abstract Monocytes and macrophages are central to atherosclerosis, but how they combine to mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients’ monocyte subtypes paired with their derived macrophage profiles were correlated with extent of CAD. Peripheral blood was collected from 40 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 the monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for the polarization markers CD86 and CD206. At baseline, patients with a greater CAD burden were older, with higher rates of statin, β‐blocker and antiplatelet drug use, whereas other characteristics were similar across the spectrum of coronary disease. CD16+ (both intermediate and non‐classical) monocytes were elevated in patients with single vessel and multivessel disease compared with those without significant CAD (P < 0.05), whereas regulatory M2 macrophages (CD206+) were decreased in patients with single vessel and multivessel disease (P < 0.001). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. On multivariable linear regression, CAD severity was associated, along with age and traditional cardiovascular risk factors, with CD16+ monocytes (directly) and M2 macrophages (inversely). Circulating monocytes may influence downstream polarization of lesional macrophages, and these measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.

Immune-Mediated Inflammation in Vulnerable Atherosclerotic Plaques

“…The differences in polarization of macrophages remained even during one week in a cell culture ex vivo. Furthermore, the authors postulate that circulating monocytes may influence the polarization of lesion macrophages, and that these measures of monocyte and macrophage subtypes may hold potential as new useful biomarkers in cardiovascular disease [43].…”

MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques

“…The results showed that MMP-14 was highly expressed in ox-LDLinduced foamy macrophages, at a level of 5•2-fold higher than that in normal macrophages. To verify the association of MMP-14 expression with in ammatory macrophages, we determined changes in the M1 macrophage markers CD68 and F4/80 [44] and the classical M2 macrophage marker CD206 [45] and con rmed that CD68 and F4/80 expression was signi cantly upregulated and that of CD206 was largely suppressed in ox-LDL-induced macrophages. These trends were reversed by the treatment with the nonselective MMP inhibitor GM6001 [46], which con rmed that MMP-14 could potentially serve as a marker for macrophage in ammatory activities.…”

Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches

“…Monocytes have also been identified as potential markers of vascular dysfunction and CAD [ 147 , 148 , 149 ]. In patients with CAD, higher monocyte counts were associated with increased risk of cardiovascular events and with peripheral endothelial dysfunction measured by peripheral arterial tonometry [ 147 ].…”

“…Regarding specific monocyte subsets, in a group of CAD patients undergoing coronary artery bypass grafting, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes, which were associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular ROS production [ 148 ]. Moreover, in patients undergoing cardiac catheterization, CAD severity was directly associated with CD16+ monocytes and inversely associated with M2 macrophages, suggesting that measures of monocyte and macrophage subtypes could also be potential biomarkers in CAD [ 149 ].…”