title: Macrophage Phenotype and Function in Different Stages of Atherosclerosis.
abstract: The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for >50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to high-density lipoprotein; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and proresolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge.
authors.affiliation: From the Departments of Medicine (I.T.), Anatomy and Cell Biology (I.T.), and Physiology and Cellular Biophysics (I.T.), Columbia University, New York; and the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (K.E.B.) and Department of Pathology (K.E.B.), UW Diabetes Institute, University of Washington School of Medicine, Seattle.
authors.forename: Ira
authors.initials: I
authors.lastname: Tabas
authors.affiliation: From the Departments of Medicine (I.T.), Anatomy and Cell Biology (I.T.), and Physiology and Cellular Biophysics (I.T.), Columbia University, New York; and the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (K.E.B.) and Department of Pathology (K.E.B.), UW Diabetes Institute, University of Washington School of Medicine, Seattle. bornf@u.washington.edu.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
mesh_terms: D000818:Animals; D001158:Arteries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D060833:Cellular Microenvironment; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D002784:Cholesterol
keywords: atherosclerosis; cholesterol; foam cells; macrophage; phenotype