Cited by 154Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismFatty Acid Research and Health

Phenotypic modulation of macrophages in response to plaque lipids

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Adamson, Samantha, Leitinger, Norbert·2011·Current Opinion in Lipidology

Abstract

PURPOSE OF REVIEW: The accumulation of macrophages in the vascular wall is a hallmark of atherosclerosis. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition, and stability. In atherosclerotic plaques, macrophages encounter a microenvironment that comprises a variety of lipid oxidation products, each of which has diverse biological effects. In this review, we summarize recent advances in our understanding of the effects of plaque lipids on macrophage phenotypic polarization. RECENT FINDINGS: Atherosclerotic lesions in mice and in humans contain various macrophage phenotypes, which play different roles in mediating inflammation, the clearance of dead cells, and possibly resolution. Macrophages alter their phenotype and biological function in response to plaque lipids through the upregulation of specific sets of genes. Interaction of oxidized lipids with pattern recognition receptors and activation of the inflammasome by cholesterol crystals drive macrophages toward an inflammatory M1 phenotype. A new phenotype, Mox, develops when oxidized phospholipids activate stress response genes via Nrf2. Other lipid mediators such as nitrosylated-fatty acids and omega-3 fatty acid-derived products polarize plaque macrophages toward anti-inflammatory and proresolving phenotypes. SUMMARY: A deeper understanding of how lipids that accumulate in atherosclerotic plaques affect macrophage phenotype and function and thus atherosclerotic lesion development and stability will help to devise novel strategies for intervention.

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  • Oxidative lipoprotein modifications generate oxidized phospholipids and other lipid mediators that can induce leukocyte recruitment and activation in the arterial intima.

    “Oxidative lipoprotein modifications lead to the generation of oxidized phospholipids (oxPLs) and other lipid mediators that have the potential to influence inflammation and atherogenesis in the arterial intima by inducing leukocyte recruitment and leukocyte activation49,50.”

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Authors
Adamson, S., & Leitinger, N.
Affiliations
University of Virginia (US)
Corresponding author
Leitinger, Norbert
Venue
Current Opinion in Lipidology
Published
2011-10
Volume
22
Issue
5
Pages
335-342
ISSN
0957-9672 (ISSN-L)
OpenAlex
W2011947002
Cited by
154
References
96
Citations by year
2026: 4 · 2025: 9 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 11 · 2020: 15 · 2019: 14 · 2018: 13 · 2017: 13 · 2016: 15 · 2015: 14 · 2014: 8 · 2013: 14 · 2012: 6
FWCI
0.83
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Lipidology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01hl084422-05)
  • National Heart, Lung, and Blood Institute (R01 HL-084422)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
atherosclerosis, plaque macrophages, macrophage polarization, oxidized lipids, lipid oxidation products, Nrf2, cholesterol crystals, inflammasome, pattern recognition receptors, omega-3 fatty acids, plaque stability
MeSH terms
Animals, Humans, Inflammation, Macrophages, Oxidation-Reduction, Atherosclerosis, Lipid Metabolism

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