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The role of non-resolving inflammation in atherosclerosis
Open accessAbstract
Non-resolving inflammation drives the development of clinically dangerous atherosclerotic lesions by promoting sustained plaque inflammation, large necrotic cores, thin fibrous caps, and thrombosis. Resolution of inflammation is not merely a passive return to homeostasis, but rather an active process mediated by specific molecules, including fatty acid-derived specialized pro-resolving mediators (SPMs). In advanced atherosclerosis, there is an imbalance between levels of SPMs and proinflammatory lipid mediators, which results in sustained leukocyte influx into lesions, inflammatory macrophage polarization, and impaired efferocytosis. In animal models of advanced atherosclerosis, restoration of SPMs limits plaque progression by suppressing inflammation, enhancing efferocytosis, and promoting an increase in collagen cap thickness. This Review discusses the roles of non-resolving inflammation in atherosclerosis and highlights the unique therapeutic potential of SPMs in blocking the progression of clinically dangerous plaques.
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“Both SPMs and IL-10 promote efferocytosis36,93,181–185”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [93]
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Metadata
- Authors
- Kasikara, C., Doran, A. C., Cai, B., & Tabas, I.
- Affiliations
- Columbia University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2018-07-02
- Volume
- 128
- Issue
- 7
- Pages
- 2713-2723
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC6025992
- OpenAlex
- W2809703637
- Cited by
- 266
- References
- 135
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 28 · 2023: 37 · 2022: 43 · 2021: 46 · 2020: 39 · 2019: 25 · 2018: 7
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (17FTF33660643, 15POST25620024)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL132412, R01HL127464, P01HL087123, R01HL075662, T32HL120826)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- nonresolving inflammation, atherosclerosis, specialized pro-resolving mediators, inflammation resolution, atherosclerotic plaque, necrotic core, fibrous cap, thrombosis, macrophage polarization, efferocytosis, leukocyte influx, lipid mediators, plaque progression
- MeSH terms
- Animals, Humans, Inflammation, Models, Cardiovascular, Signal Transduction, Disease Progression, Inflammation Mediators, Atherosclerosis, Lipid Metabolism, Plaque, Atherosclerotic, Lipoxygenases
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