Cited by 1,121Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismCardiac Fibrosis and Remodeling

Macrophage Phenotype and Function in Different Stages of Atherosclerosis

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Tabas, Ira, Bornfeldt, Karin E.·2016·Circulation Research

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.

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Crossref · 10.1161/circresaha.115.306256

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  • Microenvironmental conditions such as hypoxia, acidic pH and lipoprotein-derived lipids in the arterial intima determine macrophage phenotype in atherosclerotic lesions.

    “In addition, microenvironmental conditions, such as hypoxia, acidic pH and lipoprotein-derived lipids accumulating in the arterial intima, define the phenotype of macrophages in atherosclerotic lesions26.”

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Authors
Tabas, I., & Bornfeldt, K. E.
Affiliations
University of Washington (US)
Venue
Circulation Research
Published
2016-02-19
Volume
118
Issue
4
Pages
653-667
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2276012049
Cited by
1,121
References
142
Citations by year
2026: 97 · 2025: 131 · 2024: 117 · 2023: 158 · 2022: 135 · 2021: 115 · 2020: 101 · 2019: 80 · 2018: 75 · 2017: 72 · 2016: 39
FWCI
53.66
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Public Health Service (HHSN268201000045C)
  • National Heart, Lung, and Blood Institute (P01HL092969, R01HL062887, HHSN268201000045C, R01HL075662, R01HL126028, R01HL107497)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK108209, P30DK017047)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
macrophage phenotype, atherosclerosis, monocyte-derived macrophages, macrophage plasticity, atherosclerotic plaque rupture, plaque regression, cholesterol efflux, high-density lipoprotein, macrophage migration, macrophage apoptosis, inflammatory signaling, lipid loading
MeSH terms
Animals, Arteries, Cell Differentiation, Cholesterol, Foam Cells, Humans, Macrophages, Phenotype, Signal Transduction, Inflammation Mediators, Atherosclerosis, Plaque, Atherosclerotic, Cellular Microenvironment

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