Biological profile of monocyte-derived macrophages in coronary heart disease patients: implications for plaque morphology

• Published in: Scientific reports 2019-06, Vol.9 (1), p.8680-14, Article 8680
• Main Authors: Eligini, Sonia, Cosentino, Nicola, Fiorelli, Susanna, Fabbiocchi, Franco, Niccoli, Giampaolo, Refaat, Hesham, Camera, Marina, Calligaris, Giuseppe, De Martini, Stefano, Bonomi, Alice, Veglia, Fabrizio, Fracassi, Francesco, Crea, Filippo, Marenzi, Giancarlo, Tremoli, Elena
• Format: Article
• Language: English
• Subjects: 14; 14/32; 14/63; 631/80; 692/699; 82/29; 82/51; 82/80; 96/31; Aged; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Arteriosclerosis; Atherosclerosis - diagnostic imaging; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cardiovascular disease; Cardiovascular diseases; CD163 antigen; Cell Shape; Cells, Cultured; Coronary artery; Coronary artery disease; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - metabolism; Coronary Artery Disease - pathology; Female; GTP-Binding Proteins - metabolism; Heart diseases; Heterogeneity; Humanities and Social Sciences; Humans; Inflammation; Lectins, C-Type - metabolism; Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Mannose-Binding Lectins - metabolism; Middle Aged; Monocytes; multidisciplinary; Phenotypes; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Plaques; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Thromboplastin - metabolism; Tissue factor; Tomography, Optical Coherence - methods; Transglutaminase 2; Transglutaminases - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44847-3

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.