Cited by 266Atherosclerosis and Cardiovascular DiseasesFatty Acid Research and HealthCholesterol and Lipid Metabolism

The role of non-resolving inflammation in atherosclerosis

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Kasikara, Canan, Doran, Amanda C., Cai, Bishuang, Tabas, Ira·2018·Journal of Clinical Investigation

Abstract

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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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
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
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
  • Health Sciences › Medicine › Surgery › 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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