Abstract
The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. Macrophages from coronary plaques are not available, and monocyte-derived macrophages (MDMs) are usually considered as a surrogate. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). At morphological analysis, MDMs of CAD patients had a higher prevalence of round than spindle cells, whereas in healthy subjects the prevalence of the two morphotypes was similar. Compared to healthy subjects, MDMs of CAD patients had reduced efferocytosis, lower transglutaminase-2, CD206 and CD163 receptor levels, and higher tissue factor (TF) levels. At OCT, patients with a higher prevalence of round MDMs showed more frequently a lipid-rich plaque, a thin-cap fibroatheroma, a greater intra-plaque macrophage accumulation, and a ruptured plaque. The MDM efferocytosis correlated with minimal lumen area, and TF levels in MDMs correlated with the presence of ruptured plaque. MDMs obtained from CAD patients are characterized by a morpho-phenotypic heterogeneity with a prevalence of round cells, showing pro-inflammatory and pro-thrombotic properties. The MDM profile allows identifying CAD patients at high risk.
Highlights
The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability
We have previously reported that monocytes isolated from healthy subjects and spontaneously differentiated into macrophages (MDMs) give rise to two dominant morphotypes coexisting in the same culture, namely round monocyte-derived macrophages (MDMs) showing a non-inflammatory and reparative phenotype, and spindle MDMs exhibiting a pro-inflammatory profile[10]
We show for the first time that the spontaneous in vitro differentiation of monocytes into MDMs of coronary artery disease (CAD) patients results in a higher prevalence of round MDMs, having a lower efferocytic capacity and an enhanced thrombin generation capacity, as compared to healthy subjects
Summary
The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). In experimental models and human atherosclerotic lesions, macrophages display morpho-phenotypic heterogeneity, with distinct subpopulations showing pro-inflammatory or reparative properties[1,4,5,6,7]. On these premises, it has been hypothesized that the prevalence of a specific macrophage phenotype may exert harmful or beneficial functions in the progression and/or destabilization of the atherosclerotic plaque[8,9]. We evaluated whether these in vitro information reflected the in vivo morphology features of coronary plaques along with their macrophage content in acute and chronic CAD patients undergoing OCT assessment
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