title: M1 and M2 macrophage proteolytic and angiogenic profile analysis in atherosclerotic patients reveals a distinctive profile in type 2 diabetes.
abstract: 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.
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Roma-Lavisse
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Madjid
authors.initials: M
authors.lastname: Tagzirt
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Zawadzki
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lorenzi
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: André
authors.initials: A
authors.lastname: Vincentelli
authors.affiliation: Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Haulon
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Juthier
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Rauch
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Corseaux
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Belle
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Susen
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.affiliation: INSERM U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Cardiovascular and Pulmonary and Haematology Departments, University Hospital, Lille, France annabelle.dupont-2@univ-lille2.fr.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Dupont
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002533:Cerebral Angiography; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics*; D064446:Orexin Receptors; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011446:Prospective Studies; D059748:Proteolysis; D011956:Receptors, Cell Surface / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000954:Antigens, Surface; C477337:CD200R1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; C508609:IL10 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D064446:Orexin Receptors; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; C051321:SERPINE1 protein, human; C449926:STAB1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C021240:tissue-factor-pathway inhibitor 2; C064015:factor XIII subunit A; D016753:Interleukin-10; D005176:Factor XIII; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Macrophage polarization; angiogenesis; atherosclerosis; diabetes; plaque vulnerability; proteolysis