{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:07:02Z","timestamp":1792069622640,"version":"4.4.0"},"reference-count":133,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL138163"],"award-info":[{"award-number":["HL138163"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE14-0017-01"],"award-info":[{"award-number":["ANR-17-CE14-0017-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-19-ECVD-0005-01"],"award-info":[{"award-number":["ANR-19-ECVD-0005-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Atherosclerotic lesions progress through the continued recruitment of circulating blood monocytes that differentiate into macrophages within plaque. Lesion-associated macrophages are the primary immune cells present in plaque, where they take up cholesterol and store lipids in the form of small droplets resulting in a unique morphology termed foam cell. Recent scientific advances have used single-cell gene expression profiling, live-cell imaging, and fate mapping approaches to describe macrophage and monocyte contributions to pro- or anti-inflammatory mechanisms, in addition to functions of motility and proliferation within lesions. Yet, many questions regarding tissue-specific regulation of monocyte-to-macrophage differentiation and the contribution of recruited monocytes at stages of atherosclerotic disease progression remain unknown. In this review, we highlight recent advances regarding the role of monocyte and macrophage dynamics in atherosclerotic disease and identify gaps in knowledge that we hope will allow for advancing therapeutic treatment or prevention strategies for cardiovascular disease.<\/jats:p>","DOI":"10.3390\/cells10010015","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T09:02:44Z","timestamp":1608800564000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Monocyte Recruitment, Specification, and Function in Atherosclerosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-4389","authenticated-orcid":false,"given":"Ki-Wook","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"INSERM U1065, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire C3M, Universit\u00e9 C\u00f4te Azur, 06204 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3815-0891","authenticated-orcid":false,"given":"Jesse W.","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Immunology, Department of Integrative Biology &amp; Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"ref_1","first-page":"503","article-title":"MMP inhibition and the development of cerebrovascular atherosclerosis: The road ahead","volume":"33","author":"Napoli","year":"2002","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics\u20142019 update: A report from the American heart association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An Inflammatory Disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1042\/CS20180306","article-title":"Atherosclerosis and inflammation: Overview and updates","volume":"132","author":"Geovanini","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1161\/CIRCRESAHA.114.301174","article-title":"Mechanisms That Regulate Macrophage Burden in Atherosclerosis","volume":"114","author":"Randolph","year":"2014","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1182\/blood.V74.7.2527.2527","article-title":"Identification and characterization of a novel monocyte subpopulation in human peripheral blood","volume":"74","author":"Passlick","year":"1989","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/0167-5699(96)10029-3","article-title":"Heterogeneity of human blood monocytes: The CD14+CD16+ subpopulation","volume":"17","year":"1996","journal-title":"Immunol. Today"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","article-title":"Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion","volume":"20","author":"Jung","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1161\/ATVBAHA.108.180505","article-title":"Regulation of the Migration and Survival of Monocyte Subsets by Chemokine Receptors and Its Relevance to Atherosclerosis","volume":"29","author":"Gautier","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1182\/blood-2009-07-235028","article-title":"Comparison of gene expression profiles between human and mouse monocyte subsets","volume":"115","author":"Ingersoll","year":"2010","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.1117729","article-title":"A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells","volume":"311","author":"Fogg","year":"2006","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1084\/jem.20160800","article-title":"CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses","volume":"213","author":"Chong","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.immuni.2017.10.021","article-title":"Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes","volume":"47","author":"Coetzee","year":"2017","journal-title":"Immunity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.3389\/fimmu.2019.01642","article-title":"The Ontogeny of Monocyte Subsets","volume":"10","author":"Wolf","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.cell.2019.08.009","article-title":"Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells","volume":"178","author":"Liu","year":"2019","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eaaw3381","DOI":"10.1126\/science.aaw3381","article-title":"Lineage tracing on transcriptional landscapes links state to fate during differentiation","volume":"367","author":"Weinreb","year":"2020","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1172\/JCI28549","article-title":"Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques","volume":"117","author":"Tacke","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10340","DOI":"10.1073\/pnas.0604260103","article-title":"Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease","volume":"103","author":"Swirski","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.jacc.2012.07.019","article-title":"CD14++CD16+ Monocytes Independently Predict Cardiovascular Events","volume":"60","author":"Rogacev","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1161\/CIRCRESAHA.117.311519","article-title":"Thermoneutrality but Not UCP1 Deficiency Suppresses Monocyte Mobilization into Blood","volume":"121","author":"Williams","year":"2017","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1161\/CIRCRESAHA.116.303550","article-title":"Lifestyle effects on hematopoiesis and atherosclerosis","volume":"116","author":"Nahrendorf","year":"2015","journal-title":"Circ. Res."},{"key":"ref_23","first-page":"383","article-title":"Sleep modulates haematopoiesis and protects against atherosclerosis","volume":"566","author":"McAlpine","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nm.3589","article-title":"Chronic variable stress activates hematopoietic stem cells","volume":"20","author":"Heidt","year":"2014","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.cell.2019.07.050","article-title":"Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool","volume":"178","author":"Jordan","year":"2019","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1161\/CIRCULATIONAHA.111.061986","article-title":"Extramedullary Hematopoiesis Generates Ly-6ChighMonocytes That Infiltrate Atherosclerotic Lesions","volume":"125","author":"Robbins","year":"2012","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.immuni.2012.12.001","article-title":"Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis","volume":"38","author":"Yona","year":"2013","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1084\/jem.20170355","article-title":"The fate and lifespan of human monocyte subsets in steady state and systemic inflammation","volume":"214","author":"Patel","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shchukina, I., Bagaitkar, J., Shpynov, O., Loginicheva, E., Porter, S., Mogilenko, D.A., Wolin, E., Collins, P., Demidov, G., and Artomov, M. (2020). Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome. Nat. Aging, 1\u201318.","DOI":"10.1038\/s43587-020-00002-6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2016.10.011","article-title":"Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6Clow Monocytes while Preserving Macrophage Gene Function","volume":"45","author":"Thomas","year":"2016","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.immuni.2017.04.018","article-title":"Genomic Characterization of Murine Monocytes Reveals C\/EBP\u03b2 Transcription Factor Dependence of Ly6C\u2014Cells","volume":"46","author":"Mildner","year":"2017","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/ni.2063","article-title":"The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C\u2212 monocytes","volume":"12","author":"Hanna","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.cell.2013.03.010","article-title":"Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal","volume":"153","author":"Carlin","year":"2013","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12597","DOI":"10.1038\/ncomms12597","article-title":"Regulation of monocyte cell fate by blood vessels mediated by Notch signalling","volume":"7","author":"Gamrekelashvili","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1142883","article-title":"Monitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior","volume":"317","author":"Auffray","year":"2007","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1182\/blood-2011-04-348946","article-title":"In vivo structure\/function and expression analysis of the CX3C chemokine fractalkine","volume":"118","author":"Kim","year":"2011","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11843-0","article-title":"Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung","volume":"10","author":"Schyns","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1161\/CIRCRESAHA.117.310739","article-title":"Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis","volume":"120","author":"Quintar","year":"2017","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1161\/ATVBAHA.117.309123","article-title":"Scavenger Receptor CD36 Directs Nonclassical Monocyte Patrolling Along the Endothelium During Early Atherogenesis","volume":"37","author":"Marcovecchio","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1161\/CIRCRESAHA.117.311021","article-title":"A Polecat\u2019s View of Patrolling Monocytes","volume":"120","author":"Williams","year":"2017","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1161\/CIRCRESAHA.111.253377","article-title":"NR4A1 (Nur77) Deletion Polarizes Macrophages Toward an Inflammatory Phenotype and Increases Atherosclerosis","volume":"110","author":"Hanna","year":"2012","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s12192-018-0886-1","article-title":"NR4A1 contributes to high-fat associated endothelial dysfunction by promoting CaMKII-Parkin-mitophagy pathways","volume":"23","author":"Li","year":"2018","journal-title":"Cell Stress Chaperon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/JLB.4HI0420-098R","article-title":"Frontline Science: Kindlin-3 is essential for patrolling and phagocytosis functions of nonclassical monocytes during metastatic cancer surveillance","volume":"107","author":"Marcovecchio","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1084\/jem.20160486","article-title":"MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes","volume":"213","author":"Kim","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1016\/j.jacc.2018.08.2148","article-title":"Macrophage Biology, Classification, and Phenotype in Cardiovascular Disease","volume":"72","author":"Williams","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/ni.3343","article-title":"Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth","volume":"17","author":"Ensan","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18287-x","article-title":"Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation","volume":"11","author":"Weinberger","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.immuni.2013.11.019","article-title":"Embryonic and Adult-Derived Resident Cardiac Macrophages Are Maintained through Distinct Mechanisms at Steady State and during Inflammation","volume":"40","author":"Epelman","year":"2014","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1084\/jem.20131199","article-title":"Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF","volume":"210","author":"Guilliams","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1161\/CIRCRESAHA.109.200717","article-title":"Mechanisms of Transendothelial Migration of Leukocytes","volume":"105","author":"Muller","year":"2009","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8264","DOI":"10.1073\/pnas.92.18.8264","article-title":"Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E","volume":"92","author":"Smith","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1172\/JCI119891","article-title":"Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice","volume":"101","author":"Rajavashisth","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sinha, S.K., Miikeda, A., Fouladian, Z., Mehrabian, M., Edillor, C., Shih, D., Zhou, Z., Paul, M.K., Charugundla, S., and Davis, R.C. (2020). Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis. Arter. Thromb. Vasc. Biol.","DOI":"10.1161\/ATVBAHA.120.315255"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.4049\/jimmunol.1800002","article-title":"MyeloidSlc2a1-Deficient Murine Model Revealed Macrophage Activation and Metabolic Phenotype Are Fueled by GLUT","volume":"202","author":"Freemerman","year":"2019","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1161\/CIRCRESAHA.115.307599","article-title":"Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE\u2212\/\u2212 Mice","volume":"118","author":"Sarrazy","year":"2016","journal-title":"Circ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1161\/ATVBAHA.111.225839","article-title":"Macrophage Mal1 Deficiency Suppresses Atherosclerosis in Low-Density Lipoprotein Receptor\u2013Null Mice by Activating Peroxisome Proliferator-Activated Receptor-\u03b3\u2013Regulated Genes","volume":"31","author":"Babaev","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1096\/fj.201700235R","article-title":"Hypoxia-inducible protein 2 Hig2\/Hilpda mediates neutral lipid accumulation in macrophages and contributes to atherosclerosis in apolipoprotein E\u2013deficient mice","volume":"31","author":"Maier","year":"2017","journal-title":"FASEB J."},{"key":"ref_58","first-page":"714","article-title":"Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release","volume":"563","author":"Morioka","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1161\/CIRCRESAHA.117.312333","article-title":"Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production","volume":"122","author":"Viaud","year":"2018","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0014-4800(79)90079-0","article-title":"The subcellular biochemistry of human arterial lesions","volume":"30","author":"Berberian","year":"1979","journal-title":"Exp. Mol. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13531","DOI":"10.1073\/pnas.1735526100","article-title":"Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading","volume":"100","author":"Rong","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nm.3866","article-title":"KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis","volume":"21","author":"Shankman","year":"2015","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nm.4109","article-title":"Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective","volume":"22","author":"Cherepanova","year":"2016","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41569-019-0227-9","article-title":"Vascular smooth muscle cells in atherosclerosis","volume":"16","author":"Basatemur","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/s41590-020-0768-4","article-title":"Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression","volume":"21","author":"Williams","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1084\/jem.20082129","article-title":"Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves","volume":"206","author":"Choi","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1084\/jem.20060245","article-title":"Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis","volume":"203","author":"Haidari","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1161\/CIRCRESAHA.109.210781","article-title":"Resident Intimal Dendritic Cells Accumulate Lipid and Contribute to the Initiation of Atherosclerosis","volume":"106","author":"Paulson","year":"2010","journal-title":"Circ. Res."},{"key":"ref_70","first-page":"894","article-title":"Decreased lesion formation in CCR2\u2212\/\u2212 mice reveals a role for chemokines in the initiation of atherosclerosis","volume":"394","author":"Boring","year":"1998","journal-title":"Nat. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1172\/JCI5624","article-title":"MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B","volume":"103","author":"Gosling","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/nm.3258","article-title":"Local proliferation dominates lesional macrophage accumulation in atherosclerosis","volume":"19","author":"Robbins","year":"2013","journal-title":"Nat. Med."},{"key":"ref_73","first-page":"668","article-title":"Active proliferative of different cell types, including lymphocytes, in human atherosclerotic plaques","volume":"147","author":"Rekhter","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_74","first-page":"1","article-title":"Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering","volume":"115","author":"Kornemann","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1172\/JCI43802","article-title":"Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe\u2212\/\u2212 mice during disease regression","volume":"121","author":"Potteaux","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.imbio.2006.05.025","article-title":"Migratory fate and differentiation of blood monocyte subsets","volume":"211","author":"Tacke","year":"2006","journal-title":"Immunobiology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1161\/ATVBAHA.118.311319","article-title":"Limited Macrophage Positional Dynamics in Progressing or Regressing Murine Atherosclerotic Plaques\u2014Brief Report","volume":"38","author":"Williams","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1161\/CIRCRESAHA.119.315175","article-title":"Migratory and Dancing Macrophage Subsets in Atherosclerotic Lesions","volume":"125","author":"McArdle","year":"2019","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1161\/CIRCRESAHA.119.315940","article-title":"Single Cell RNA-Sequencing in Atherosclerosis","volume":"126","author":"Williams","year":"2020","journal-title":"Circ. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1161\/CIRCRESAHA.117.312513","article-title":"Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry","volume":"122","author":"Winkels","year":"2018","journal-title":"Circ. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1161\/CIRCRESAHA.120.316903","article-title":"Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas","volume":"127","author":"Zernecke","year":"2020","journal-title":"Circ. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1161\/CIRCRESAHA.118.312804","article-title":"Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine Models","volume":"123","author":"Kim","year":"2018","journal-title":"Circ. Res."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zernecke, A., Erhard, F., Weinberger, T., Schulz, C., Ley, K., Saliba, A.-E., and Cochain, C. (2020). Integrated scRNA-seq analysis identifies conserved transcriptomic features of 2 mononuclear phagocytes in mouse and human atherosclerosis. bioRxiv.","DOI":"10.1101\/2020.12.09.417535"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.cell.2012.06.054","article-title":"Regulated Accumulation of Desmosterol Integrates Macrophage Lipid Metabolism and Inflammatory Responses","volume":"151","author":"Spann","year":"2012","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.4049\/jimmunol.1601363","article-title":"Oxidized Low-Density Lipoprotein Loading of Macrophages Downregulates TLR-Induced Proinflammatory Responses in a Gene-Specific and Temporal Manner through Transcriptional Control","volume":"199","author":"Zhang","year":"2017","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.immuni.2018.06.008","article-title":"Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen","volume":"49","author":"Lim","year":"2018","journal-title":"Immunity"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/s41591-019-0590-4","article-title":"Single-cell immune landscape of human atherosclerotic plaques","volume":"25","author":"Fernandez","year":"2019","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.cmet.2013.04.001","article-title":"Hyperglycemia Promotes Myelopoiesis and Impairs the Resolution of Atherosclerosis","volume":"17","author":"Nagareddy","year":"2013","journal-title":"Cell Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.stem.2014.06.002","article-title":"Glucose and Glutamine Metabolism Regulate Human Hematopoietic Stem Cell Lineage Specification","volume":"15","author":"Oburoglu","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.immuni.2015.02.005","article-title":"Network Integration of Parallel Metabolic and Transcriptional Data Reveals Metabolic Modules that Regulate Macrophage Polarization","volume":"42","author":"Jha","year":"2015","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3389\/fimmu.2019.01084","article-title":"Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS\u2013) vs. Alternatively Activated Macrophages","volume":"10","author":"Orecchioni","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1172\/JCI75005","article-title":"Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression","volume":"127","author":"Rahman","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lin, J.-D., Nishi, H., Poles, J., Niu, X., McCauley, C., Rahman, K., Brown, E.J., Yeung, S.T., Vozhilla, N., and Weinstock, A. (2019). Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression. JCI Insight, 4.","DOI":"10.1172\/jci.insight.124574"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/CIRCRESAHA.116.310262","article-title":"Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption ActivityNovelty and Significance","volume":"121","author":"Daoudi","year":"2017","journal-title":"Circ. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.2353\/ajpath.2009.080431","article-title":"Coronary Intraplaque Hemorrhage Evokes a Novel Atheroprotective Macrophage Phenotype","volume":"174","author":"Boyle","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jacc.2011.10.852","article-title":"Hemoglobin Directs Macrophage Differentiation and Prevents Foam Cell Formation in Human Atherosclerotic Plaques","volume":"59","author":"Finn","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1161\/CIRCRESAHA.113.301656","article-title":"Liver X Receptor Activation Stimulates Iron Export in Human Alternative Macrophages","volume":"113","author":"Bories","year":"2013","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1172\/JCI93025","article-title":"CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis","volume":"128","author":"Guo","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.atherosclerosis.2012.09.013","article-title":"Distribution of macrophage polarization markers in human atherosclerosis","volume":"225","author":"Gijbels","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Lawler, P.R., Bhatt, D.L., Godoy, L.C., L\u00fcscher, T.F., O Bonow, R., Verma, S., and Ridker, P.M. (2020). Targeting cardiovascular inflammation: Next steps in clinical translation. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehaa099"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.immuni.2019.03.007","article-title":"Cytokine Circuits in Cardiovascular Disease","volume":"50","author":"Williams","year":"2019","journal-title":"Immunity"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1161\/ATVBAHA.118.312037","article-title":"Chemokines as Therapeutic Targets in Cardiovascular Disease","volume":"39","author":"Noels","year":"2019","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_104","first-page":"1357","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_105","first-page":"179","article-title":"Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells","volume":"124","author":"Libby","year":"1986","journal-title":"Am. J. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1172\/JCI112732","article-title":"Inducible interleukin-1 gene expression in human vascular smooth muscle cells","volume":"78","author":"Libby","year":"1986","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1161\/CIRCRESAHA.118.314402","article-title":"Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation","volume":"125","author":"Zhuang","year":"2019","journal-title":"Circ. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.2353\/ajpath.2006.051054","article-title":"Interleukin-1\u03b2 and Signaling of Interleukin-1 in Vascular Wall and Circulating Cells Modulates the Extent of Neointima Formation in Mice","volume":"168","author":"Chamberlain","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0021-9150(99)00011-8","article-title":"Cytokine expression in advanced human atherosclerotic plaques: Dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines","volume":"145","author":"Ulfgren","year":"1999","journal-title":"Atherosclerosis"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1161\/01.ATV.16.8.1000","article-title":"Interleukin-1\u03b2 in Coronary Arteries of Patients with Ischemic Heart Disease","volume":"16","author":"Galea","year":"1996","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1172\/JCI112200","article-title":"Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines","volume":"76","author":"Bevilacqua","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_112","first-page":"394","article-title":"Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion","volume":"121","author":"Bevilacqua","year":"1985","journal-title":"Am. J. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1161\/01.ATV.0000064374.15232.C3","article-title":"Lack of Interleukin-1\u03b2 Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice","volume":"23","author":"Kirii","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/s41591-018-0124-5","article-title":"Interleukin-1\u03b2 has atheroprotective effects in advanced atherosclerotic lesions of mice","volume":"24","author":"Gomez","year":"2018","journal-title":"Nat. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/S0140-6736(12)60110-X","article-title":"The interleukin-6 receptor as a target for prevention of coronary heart disease: A mendelian randomisation analysis","volume":"379","author":"Swerdlow","year":"2012","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1161\/01.ATV.19.10.2364","article-title":"Interleukin-6 Exacerbates Early Atherosclerosis in Mice","volume":"19","author":"Huber","year":"1999","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1161\/01.CIR.0000148135.08582.97","article-title":"Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis","volume":"110","author":"Schieffer","year":"2004","journal-title":"Circulation"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/1043-4666(94)90013-2","article-title":"Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions","volume":"6","author":"Seino","year":"1994","journal-title":"Cytokine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1161\/01.CIR.101.12.1372","article-title":"Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques","volume":"101","author":"Schieffer","year":"2000","journal-title":"Circulation"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1161\/01.ATV.18.9.1498","article-title":"Expression of Interleukin-6 in Atherosclerotic Lesions of Male ApoE-Knockout Mice","volume":"18","author":"Sukovich","year":"1998","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1161\/01.ATV.0000143933.20616.1b","article-title":"Inhibition of Tumor Necrosis Factor-\u03b1 Reduces Atherosclerosis in Apolipoprotein E Knockout Mice","volume":"24","author":"Hovgaard","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.atherosclerosis.2004.11.016","article-title":"Disruption of tumor necrosis factor-\u03b1 gene diminishes the development of atherosclerosis in ApoE-deficient mice","volume":"180","author":"Ohta","year":"2005","journal-title":"Atherosclerosis"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.4049\/jimmunol.139.6.1855","article-title":"Stimulation of endothelial cell binding of lymphocytes by tumor necrosis factor","volume":"139","author":"Cavender","year":"1987","journal-title":"J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.atherosclerosis.2018.08.030","article-title":"Anti-tumor necrosis factor-\u03b1 therapy increases plaque burden in a mouse model of experimental atherosclerosis","volume":"277","author":"Oberoi","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1172\/JCI119798","article-title":"Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice","volume":"100","author":"Boring","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1172\/JCI115411","article-title":"Monocyte chemoattractant protein-1 in human atheromatous plaques","volume":"88","author":"Nelken","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1097-2765(00)80139-2","article-title":"Absence of Monocyte Chemoattractant Protein-1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor\u2013Deficient Mice","volume":"2","author":"Gu","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1161\/01.ATV.19.6.1518","article-title":"Monocyte Chemoattractant Protein-1 Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice","volume":"19","author":"Aiello","year":"1999","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1161\/CIRCULATIONAHA.105.543579","article-title":"CCL2 Polymorphisms Are Associated with Serum Monocyte Chemoattractant Protein-1 Levels and Myocardial Infarction in the Framingham Heart Study","volume":"112","author":"McDermott","year":"2005","journal-title":"Circulation"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0021-9150(01)00423-3","article-title":"Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 \u22122518 G\/G genotype in CAD patients","volume":"158","author":"Szalai","year":"2001","journal-title":"Atherosclerosis"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.amjcard.2010.11.005","article-title":"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","volume":"107","author":"Gilbert","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/CIRCULATIONAHA.112.000116","article-title":"Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice","volume":"127","author":"Majmudar","year":"2013","journal-title":"Circulation"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:45:25Z","timestamp":1760179525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,24]]},"references-count":133,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["cells10010015"],"URL":"https:\/\/doi.org\/10.3390\/cells10010015","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,24]]}}}