Functional diversity of macrophages in vascular biology and disease

Dahlof, 2010, Cardiovascular disease risk factors: epidemiology and risk assessment, Am. J. Cardiol., 105, 3A, 10.1016/j.amjcard.2009.10.007 Lloyd-Jones, 2010, Cardiovascular risk prediction: basic concepts, current status, and future directions, Circulation, 121, 1768, 10.1161/CIRCULATIONAHA.109.849166 Anitschkow, 1964, Compensatory adjustments in the structure of coronary arteries of the heart with stenotic atherosclerosis, Circulation, 29, 447, 10.1161/01.CIR.29.3.447 Goldstein, 1976, Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus, Cell, 9, 195, 10.1016/0092-8674(76)90110-0 Ross, 1993, The pathogenesis of atherosclerosis: a perspective for the 1990s, Nature, 362, 801, 10.1038/362801a0 Cybulsky, 1991, Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis, Science, 251, 788, 10.1126/science.1990440 Ross, 1999, Atherosclerosis—an inflammatory disease, N. Engl. J. Med., 340, 115, 10.1056/NEJM199901143400207 Qiao, 1997, Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice, Am. J. Pathol., 150, 1687 Rajavashisth, 1998, Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice, J. Clin. Invest., 101, 2702, 10.1172/JCI119891 Stoneman, 2007, Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques, Circ. Res., 100, 884, 10.1161/01.RES.0000260802.75766.00 Kunjathoor, 2002, Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages, J. Biol. Chem., 277, 49982, 10.1074/jbc.M209649200 Ball, 1995, Evidence that the death of macrophage foam cells contributes to the lipid core of atheroma, Atherosclerosis, 114, 45, 10.1016/0021-9150(94)05463-S Virmani, 2002, Vulnerable plaque: the pathology of unstable coronary lesions, J. Interv. Cardiol., 15, 439, 10.1111/j.1540-8183.2002.tb01087.x Arai, 2005, A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development, Cell Metab., 1, 201, 10.1016/j.cmet.2005.02.002 Gautier, 2009, Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage, Circulation, 119, 1795, 10.1161/CIRCULATIONAHA.108.806158 Liu, 2005, Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice, Arterioscler. Thromb. Vasc. Biol., 25, 174, 10.1161/01.ATV.0000148548.47755.22 Park, 2011, Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein, Nature, 477, 220, 10.1038/nature10340 Hume, 2006, The mononuclear phagocyte system, Curr. Opin. Immunol., 18, 49, 10.1016/j.coi.2005.11.008 Boyle, 2012, Heme and haemoglobin direct macrophage Mhem phenotype and counter foam cell formation in areas of intraplaque haemorrhage, Curr. Opin. Lipidol., 23, 453, 10.1097/MOL.0b013e328356b145 Chinetti-Gbaguidi, 2011, Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARgamma and LXRalpha pathways, Circ. Res., 108, 985, 10.1161/CIRCRESAHA.110.233775 Erbel, 2015, Prevalence of M4 macrophages within human coronary atherosclerotic plaques is associated with features of plaque instability, Int. J. Cardiol., 186, 219, 10.1016/j.ijcard.2015.03.151 Finn, 2012, Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques, J. Am. Coll. Cardiol., 59, 166, 10.1016/j.jacc.2011.10.852 Gleissner, 2010, CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages, Circ. Res., 106, 203, 10.1161/CIRCRESAHA.109.199505 Kadl, 2010, Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2, Circ. Res., 107, 737, 10.1161/CIRCRESAHA.109.215715 Seneviratne, 2017, Interferon regulatory factor 5 controls necrotic core formation in atherosclerotic lesions by impairing efferocytosis, Circulation, 10.1161/CIRCULATIONAHA.117.027844 Stoger, 2012, Distribution of macrophage polarization markers in human atherosclerosis, Atherosclerosis, 225, 461, 10.1016/j.atherosclerosis.2012.09.013 Gosselin, 2014, Environment drives selection and function of enhancers controlling tissue-specific macrophage identities, Cell, 159, 1327, 10.1016/j.cell.2014.11.023 Lavin, 2014, Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment, Cell, 159, 1312, 10.1016/j.cell.2014.11.018 Ginhoux, 2010, Fate mapping analysis reveals that adult microglia derive from primitive macrophages, Science, 330, 841, 10.1126/science.1194637 Yona, 2013, Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis, Immunity, 38, 79, 10.1016/j.immuni.2012.12.001 Mosmann, 1987, Two types of mouse helper T-cell clone. Implications for immune regulation, Immunol. Today, 8, 223, 10.1016/0167-5699(87)90171-X Stein, 1992, Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation, J. Exp. Med., 176, 287, 10.1084/jem.176.1.287 Mills, 2000, M-1/M-2 macrophages and the Th1/Th2 paradigm, J. Immunol., 164, 6166, 10.4049/jimmunol.164.12.6166 Sans-Fons, 2013, Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of Slc7a2 (CAT2), and susceptibility to Leishmania infection is reduced, J Infect Dis, 207, 1684, 10.1093/infdis/jit084 Biswas, 2010, Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm, Nat. Immunol., 11, 889, 10.1038/ni.1937 Moore, 2013, Macrophages in atherosclerosis: a dynamic balance, Nat. Rev. Immunol., 13, 709, 10.1038/nri3520 Mosser, 2008, Exploring the full spectrum of macrophage activation, Nat. Rev. Immunol., 8, 958, 10.1038/nri2448 Piccolo, 2017, Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk, Nat. Immunol., 18, 530, 10.1038/ni.3710 Murray, 2014, Macrophage activation and polarization: nomenclature and experimental guidelines, Immunity, 41, 14, 10.1016/j.immuni.2014.06.008 Lawrence, 2011, Transcriptional regulation of macrophage polarization: enabling diversity with identity, Nat. Rev. Immunol., 11, 750, 10.1038/nri3088 Fleetwood, 2007, Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation, J. Immunol., 178, 5245, 10.4049/jimmunol.178.8.5245 Krausgruber, 2011, IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses, Nat. Immunol., 12, 231, 10.1038/ni.1990 Satoh, 2010, The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection, Nat. Immunol., 11, 936, 10.1038/ni.1920 Bain, 2014, Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice, Nat. Immunol., 15, 929, 10.1038/ni.2967 Epelman, 2014, Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation, Immunity, 40, 91, 10.1016/j.immuni.2013.11.019 Guilliams, 2013, Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF, J. Exp. Med., 210, 1977, 10.1084/jem.20131199 Ajami, 2007, Local self-renewal can sustain CNS microglia maintenance and function throughout adult life, Nat. Neurosci., 10, 1538, 10.1038/nn2014 Epelman, 2014, Origin and functions of tissue macrophages, Immunity, 41, 21, 10.1016/j.immuni.2014.06.013 Paolicelli, 2011, Synaptic pruning by microglia is necessary for normal brain development, Science, 333, 1456, 10.1126/science.1202529 Lambrecht, 2006, Alveolar macrophage in the driver's seat, Immunity, 24, 366, 10.1016/j.immuni.2006.03.008 Bruttger, 2015, Genetic cell ablation reveals clusters of local self-renewing microglia in the mammalian central nervous system, Immunity, 43, 92, 10.1016/j.immuni.2015.06.012 Schneider, 2014, Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages, Nat. Immunol., 15, 1026, 10.1038/ni.3005 Smythies, 2005, Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity, J. Clin. Invest., 115, 66, 10.1172/JCI200519229 Hashimoto, 2013, Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes, Immunity, 38, 792, 10.1016/j.immuni.2013.04.004 Scott, 2016, Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells, Nat. Commun., 7, 10.1038/ncomms10321 van de Laar, 2016, Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages, Immunity, 44, 755, 10.1016/j.immuni.2016.02.017 Nerlov, 1998, PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors, Genes Dev., 12, 2403, 10.1101/gad.12.15.2403 Olson, 1995, PU. 1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation, Immunity, 3, 703, 10.1016/1074-7613(95)90060-8 Gautier, 2012, Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages, Nat. Immunol., 13, 1118, 10.1038/ni.2419 Speliotes, 1996, Myocyte-specific enhancer binding factor 2C expression in gerbil brain following global cerebral ischemia, Neuroscience, 70, 67, 10.1016/0306-4522(95)00301-X Kohyama, 2009, Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis, Nature, 457, 318, 10.1038/nature07472 N, 2013, The nuclear receptor LXRalpha controls the functional specialization of splenic macrophages, Nat. Immunol., 14, 831, 10.1038/ni.2622 Hulsmans, 2017, Macrophages facilitate electrical conduction in the heart, Cell, 169, 510, 10.1016/j.cell.2017.03.050 Pinto, 2012, An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile, PLoS One, 7, 10.1371/journal.pone.0036814 Heidt, 2014, Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction, Circ. Res., 115, 284, 10.1161/CIRCRESAHA.115.303567 Molawi, 2014, Progressive replacement of embryo-derived cardiac macrophages with age, J. Exp. Med., 211, 2151, 10.1084/jem.20140639 Ensan, 2016, Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth, Nat. Immunol., 17, 159, 10.1038/ni.3343 Averill, 1989, Enhanced monocyte progenitor cell proliferation in bone marrow of hyperlipemic swine, Am. J. Pathol., 135, 369 Back, 1995, Deposition pattern of monocytes and fatty streak development in hypercholesterolemic rabbits, Atherosclerosis, 116, 103, 10.1016/0021-9150(95)05533-3 Murphy, 2011, ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice, J. Clin. Invest., 121, 4138, 10.1172/JCI57559 Geissmann, 2003, Blood monocytes consist of two principal subsets with distinct migratory properties, Immunity, 19, 71, 10.1016/S1074-7613(03)00174-2 Ingersoll, 2010, Comparison of gene expression profiles between human and mouse monocyte subsets, Blood, 115, e10, 10.1182/blood-2009-07-235028 Ley, 2011, Monocyte and macrophage dynamics during atherogenesis, Arterioscler. Thromb. Vasc. Biol., 31, 1506, 10.1161/ATVBAHA.110.221127 Passlick, 1989, Identification and characterization of a novel monocyte subpopulation in human peripheral blood, Blood, 74, 2527, 10.1182/blood.V74.7.2527.2527 Wong, 2012, The three human monocyte subsets: implications for health and disease, Immunol. Res., 53, 41, 10.1007/s12026-012-8297-3 Swirski, 2007, Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata, J. Clin. Invest., 117, 195, 10.1172/JCI29950 Hanna, 2011, The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes, Nat. Immunol., 12, 778, 10.1038/ni.2063 Chao, 2013, Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice, J. Lipid Res., 54, 806, 10.1194/jlr.M034157 Hamers, 2012, Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis, Circ. Res., 110, 428, 10.1161/CIRCRESAHA.111.260760 Hanna, 2012, NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis, Circ. Res., 110, 416, 10.1161/CIRCRESAHA.111.253377 Hilgendorf, 2015, Monocyte fate in atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 35, 272, 10.1161/ATVBAHA.114.303565 Thomas, 2017, Human blood monocyte subsets: a new gating strategy defined using cell surface markers identified by mass cytometry, Arterioscler. Thromb. Vasc. Biol., 10.1161/ATVBAHA.117.309145 Tacke, 2007, Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques, J. Clin. Invest., 117, 185, 10.1172/JCI28549 Boring, 1998, Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis, Nature, 394, 894, 10.1038/29788 Combadiere, 2003, Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice, Circulation, 107, 1009, 10.1161/01.CIR.0000057548.68243.42 Combadiere, 2008, Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice, Circulation, 117, 1649, 10.1161/CIRCULATIONAHA.107.745091 Lesnik, 2003, Decreased atherosclerosis in CX3CR1−/− mice reveals a role for fractalkine in atherogenesis, J. Clin. Invest., 111, 333, 10.1172/JCI15555 Guo, 2005, Repopulation of apolipoprotein E knockout mice with CCR2-deficient bone marrow progenitor cells does not inhibit ongoing atherosclerotic lesion development, Arterioscler. Thromb. Vasc. Biol., 25, 1014, 10.1161/01.ATV.0000163181.40896.42 Robbins, 2013, Local proliferation dominates lesional macrophage accumulation in atherosclerosis, Nat. Med., 19, 1166, 10.1038/nm.3258 Rahman, 2017, Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression, J. Clin. Invest., 127, 2904, 10.1172/JCI75005 Auffray, 2009, Blood monocytes: development, heterogeneity, and relationship with dendritic cells, Annu. Rev. Immunol., 27, 669, 10.1146/annurev.immunol.021908.132557 Bouhlel, 2007, PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties, Cell Metab., 6, 137, 10.1016/j.cmet.2007.06.010 Cho, 2013, The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery, J. Stroke Cerebrovasc. Dis., 22, 910, 10.1016/j.jstrokecerebrovasdis.2012.11.020 Shalhoub, 2016, Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques, Thromb. Haemost., 115, 1064, 10.1160/TH15-08-0650 Jiang, 1998, PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines, Nature, 391, 82, 10.1038/34184 Liao, 2011, Kruppel-like factor 4 regulates macrophage polarization, J. Clin. Invest., 121, 2736, 10.1172/JCI45444 Ricote, 1998, The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation, Nature, 391, 79, 10.1038/34178 Babaev, 2005, Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice, Arterioscler. Thromb. Vasc. Biol., 25, 1647, 10.1161/01.ATV.0000173413.31789.1a Collins, 2001, Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice, Arterioscler. Thromb. Vasc. Biol., 21, 365, 10.1161/01.ATV.21.3.365 Li, 2000, Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice, J. Clin. Invest., 106, 523, 10.1172/JCI10370 Sharma, 2012, Myeloid Kruppel-like factor 4 deficiency augments atherogenesis in ApoE−/− mice—brief report, Arterioscler. Thromb. Vasc. Biol., 32, 2836, 10.1161/ATVBAHA.112.300471 Venkateswaran, 2000, Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha, Proc. Natl. Acad. Sci. U. S. A., 97, 12097, 10.1073/pnas.200367697 Spann, 2012, Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses, Cell, 151, 138, 10.1016/j.cell.2012.06.054 Galis, 1995, Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases, Proc. Natl. Acad. Sci. U. S. A., 92, 402, 10.1073/pnas.92.2.402 Johnson, 2008, Low tissue inhibitor of metalloproteinases 3 and high matrix metalloproteinase 14 levels defines a subpopulation of highly invasive foam-cell macrophages, Arterioscler. Thromb. Vasc. Biol., 28, 1647, 10.1161/ATVBAHA.108.170548 Thomas, 2007, Genomics of foam cells and nonfoamy macrophages from rabbits identifies arginase-I as a differential regulator of nitric oxide production, Arterioscler. Thromb. Vasc. Biol., 27, 571, 10.1161/01.ATV.0000256470.23842.94 Thomas, 2015, Foam cell formation in vivo converts macrophages to a pro-fibrotic phenotype, PLoS One, 10, 10.1371/journal.pone.0128163 Hayes, 2014, Classical and alternative activation and metalloproteinase expression occurs in foam cell macrophages in male and female ApoE null mice in the absence of T and B lymphocytes, Front. Immunol., 5, 537, 10.3389/fimmu.2014.00537 Chinetti-Gbaguidi, 2015, Macrophage subsets in atherosclerosis, Nat. Rev. Cardiol., 12, 10, 10.1038/nrcardio.2014.173 Stewart, 2010, CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer, Nat. Immunol., 11, 155, 10.1038/ni.1836 Duewell, 2010, NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals, Nature, 464, 1357, 10.1038/nature08938 Levy, 2006, Intraplaque hemorrhage, Curr. Mol. Med., 6, 479, 10.2174/156652406778018626 Boyle, 2009, Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype, Am. J. Pathol., 174, 1097, 10.2353/ajpath.2009.080431 Boyle, 2011, Heme induces heme oxygenase 1 via Nrf2: role in the homeostatic macrophage response to intraplaque hemorrhage, Arterioscler. Thromb. Vasc. Biol., 31, 2685, 10.1161/ATVBAHA.111.225813 Boyle, 2012, Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection, Circ. Res., 110, 20, 10.1161/CIRCRESAHA.111.247577 Pitsilos, 2003, Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters, Thromb. Haemost., 90, 1112, 10.1160/TH03-02-0069 Sachais, 2007, Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE−/− mice, Thromb. Haemost., 98, 1108 Erbel, 2015, CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+ in vitro and in vivo, Innate Immun., 21, 255, 10.1177/1753425914526461 Cho, 2007, Induction of dendritic cell-like phenotype in macrophages during foam cell formation, Physiol. Genomics, 29, 149, 10.1152/physiolgenomics.00051.2006 Jongstra-Bilen, 2006, Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis, J. Exp. Med., 203, 2073, 10.1084/jem.20060245 Wu, 2009, Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia, Circulation, 119, 2708, 10.1161/CIRCULATIONAHA.108.823740 Wentworth, 2010, Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity, Diabetes, 59, 1648, 10.2337/db09-0287 Arnold, 2016, CD11c(+) monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23, Mucosal Immunol., 9, 352, 10.1038/mi.2015.65 Feil, 2014, Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis, Circ. Res., 115, 662, 10.1161/CIRCRESAHA.115.304634 Gomez, 2012, Smooth muscle cell phenotypic switching in atherosclerosis, Cardiovasc. Res., 95, 156, 10.1093/cvr/cvs115 Strobl, 1998, Identification of CD68+lin- peripheral blood cells with dendritic precursor characteristics, J. Immunol., 161, 740, 10.4049/jimmunol.161.2.740 Parwaresch, 1986, Monocyte/macrophage-reactive monoclonal antibody Ki-M6 recognizes an intracytoplasmic antigen, Am. J. Pathol., 125, 141 Andreeva, 1997, Subendothelial smooth muscle cells of human aorta express macrophage antigen in situ and in vitro, Atherosclerosis, 135, 19, 10.1016/S0021-9150(97)00136-6 Back, 2015, Anti-inflammatory therapies for atherosclerosis, Nat. Rev. Cardiol., 12, 199, 10.1038/nrcardio.2015.5 Ridker, 2010, Statin therapy for low-LDL, high-hsCRP patients: from JUPITER to CORONA, Clin. Chem., 56, 505, 10.1373/clinchem.2009.142653 Sabatine, 2017, Investigators, evolocumab and clinical outcomes in patients with cardiovascular disease, N. Engl. J. Med., 376, 1713, 10.1056/NEJMoa1615664 Micha, 2011, Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease, Am. J. Cardiol., 108, 1362, 10.1016/j.amjcard.2011.06.054 Ridker, 2017, Antiinflammatory therapy with canakinumab for atherosclerotic disease, N. Engl. J. Med., 10.1056/NEJMoa1707914 Tabas, 2010, Macrophage death and defective inflammation resolution in atherosclerosis, Nat. Rev. Immunol., 10, 36, 10.1038/nri2675 Thorp, 2009, Mechanisms and consequences of efferocytosis in advanced atherosclerosis, J. Leukoc. Biol., 86, 1089, 10.1189/jlb.0209115 Schrijvers, 2005, Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 25, 1256, 10.1161/01.ATV.0000166517.18801.a7 Kojima, 2016, CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis, Nature, 536, 86, 10.1038/nature18935 Cai, 2017, MerTK receptor cleavage promotes plaque necrosis and defective resolution in atherosclerosis, J. Clin. Invest., 127, 564, 10.1172/JCI90520 Zizzo, 2015, The PPAR-gamma antagonist GW9662 elicits differentiation of M2c-like cells and upregulation of the MerTK/Gas6 axis: a key role for PPAR-gamma in human macrophage polarization, J. Inflamm. (Lond.), 12, 36, 10.1186/s12950-015-0081-4 de Jong, 2017, Protective aptitude of annexin A1 in arterial neointima formation in atherosclerosis-prone mice-brief report, Arterioscler. Thromb. Vasc. Biol., 37, 312, 10.1161/ATVBAHA.116.308744 Schultze, 2016, Reprogramming of macrophages—new opportunities for therapeutic targeting, Curr. Opin. Pharmacol., 26, 10, 10.1016/j.coph.2015.09.007 Bendall, 2011, Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum, Science, 332, 687, 10.1126/science.1198704 Dawson, 1999, Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice, Atherosclerosis, 143, 205, 10.1016/S0021-9150(98)00318-9 Veillard, 2005, Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo, Circulation, 112, 870, 10.1161/CIRCULATIONAHA.104.520718 Gilbert, 2011, Effect of CC chemokine receptor 2 CCR2 blockade on serum C-reactive protein in individuals at atherosclerotic risk and with a single nucleotide polymorphism of the monocyte chemoattractant protein-1 promoter region, Am. J. Cardiol., 107, 906, 10.1016/j.amjcard.2010.11.005 Bot, 2017, A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy, Sci. Rep., 7, 52, 10.1038/s41598-017-00104-z Cheng, 2007, Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines, J. Clin. Invest., 117, 616, 10.1172/JCI28180 Kirii, 2003, Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice, Arterioscler. Thromb. Vasc. Biol., 23, 656, 10.1161/01.ATV.0000064374.15232.C3 Davenport, 2003, The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice, Am. J. Pathol., 163, 1117, 10.1016/S0002-9440(10)63471-2 Ryan, 2011, Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials, JAMA, 306, 864, 10.1001/jama.2011.1211 Tzellos, 2013, Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials, J. Eur. Acad. Dermatol. Venereol., 27, 622, 10.1111/j.1468-3083.2012.04500.x Lee, 1999, The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice, Arterioscler. Thromb. Vasc. Biol., 19, 734, 10.1161/01.ATV.19.3.734 Branen, 2004, Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice, Arterioscler. Thromb. Vasc. Biol., 24, 2137, 10.1161/01.ATV.0000143933.20616.1b Ohta, 2005, Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice, Atherosclerosis, 180, 11, 10.1016/j.atherosclerosis.2004.11.016 Busard, 2017, Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial, Trials, 18, 52, 10.1186/s13063-017-1777-y Jacobsson, 2005, Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis, J. Rheumatol., 32, 1213 Schieffer, 2004, Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis, Circulation, 110, 3493, 10.1161/01.CIR.0000148135.08582.97 Kleveland, 2016, Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial, Eur. Heart J., 37, 2406, 10.1093/eurheartj/ehw171 Schuster, 2002, Accumulation of foam cells in liver X receptor-deficient mice, Circulation, 106, 1147, 10.1161/01.CIR.0000026802.79202.96 Bischoff, 2010, Non-redundant roles for LXRalpha and LXRbeta in atherosclerosis susceptibility in low density lipoprotein receptor knockout mice, J. Lipid Res., 51, 900 Joseph, 2002, Synthetic LXR ligand inhibits the development of atherosclerosis in mice, Proc. Natl. Acad. Sci. U. S. A., 99, 7604, 10.1073/pnas.112059299 Courties, 2014, In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing, J. Am. Coll. Cardiol., 63, 1556, 10.1016/j.jacc.2013.11.023