Macrophage Phenotype and Function in Different Stages of Atherosclerosis
Open accessAbstract
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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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.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [26]
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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
- PMC
- PMC4762068
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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