M1 and M2 macrophage proteolytic and angiogenic profile analysis in atherosclerotic patients reveals a distinctive profile in type 2 diabetes

• Published in: Diabetes & vascular disease research 2015-07, Vol.12 (4), p.279-289
• Main Authors: Roma-Lavisse, Charlotte, Tagzirt, Madjid, Zawadzki, Christophe, Lorenzi, Rodrigo, Vincentelli, André, Haulon, Stephan, Juthier, Francis, Rauch, Antoine, Corseaux, Delphine, Staels, Bart, Jude, Brigitte, Van Belle, Eric, Susen, Sophie, Chinetti-Gbaguidi, Giulia, Dupont, Annabelle
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Surface - genetics; Atherosclerosis - complications; Atherosclerosis - diagnostic imaging; Atherosclerosis - genetics; Carotid Artery Diseases - complications; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - genetics; Case-Control Studies; Cell Adhesion Molecules, Neuronal - genetics; Cerebral Angiography; Coronary Angiography; Coronary Artery Disease - complications; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - genetics; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Factor XIII - genetics; Female; Gene Expression Regulation; Glycoproteins - genetics; Humans; Interleukin-10 - genetics; Interleukin-1beta - genetics; Lectins, C-Type - genetics; Macrophages - metabolism; Male; Mannose-Binding Lectins - genetics; Matrix Metalloproteinase 9 - genetics; Middle Aged; Neovascularization, Pathologic - genetics; Phenotype; Plasminogen Activator Inhibitor 1 - genetics; Prospective Studies; Proteolysis; Receptors, Cell Surface - genetics; Receptors, Lymphocyte Homing - genetics; Reverse Transcriptase Polymerase Chain Reaction; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1479-1641; 1752-8984
• DOI: 10.1177/1479164115582351

This study aimed to investigate atherosclerotic mediators’ expression levels in M1 and M2 macrophages and to focus on the influence of diabetes on M1/M2 profiles. Macrophages from 36 atherosclerotic patients (19 diabetics and 17 non-diabetics) were cultured with interleukin-1β (IL-1β) or IL-4 to induce M1 or M2 phenotype, respectively. The atherosclerotic mediators’ expression was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that M1 and M2 macrophages differentially expressed mediators involved in proteolysis and angiogenesis processes. The proteolytic balance (matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-9/plasminogen activator inhibitor-1 (PAI-1) and MMP-9/tissue factor pathway inhibitor-2 (TFPI-2) ratios) was higher in M1 versus M2, whereas M2 macrophages presented higher angiogenesis properties (increased vascular endothelial growth factor/TFPI-2 and tissue factor/TFPI-2 ratios). Moreover, M1 macrophages from diabetics displayed more important proangiogenic and proteolytic activities than non-diabetics. This study reveals that M1 and M2 macrophages could differentially modulate major atherosclerosis-related pathological processes. Moreover, M1 macrophages from diabetics display a deleterious phenotype that could explain the higher plaque vulnerability observed in these subjects.