Cited by 415Fatty Acid Research and HealthAtherosclerosis and Cardiovascular DiseasesEicosanoids and Hypertension Pharmacology

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Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators

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Merched, Aksam J., Ko, Kerry, Gotlinger, Katherine H., Serhan, Charles N., Chan, Lawrence·2008·The FASEB Journal

DOI 10.1096/fj.08-112201PMC PMC2537438

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Abstract

Atherosclerosis is now recognized as an inflammatory disease involving the vascular wall. Recent results indicate that acute inflammation does not simply passively resolve as previously assumed but is actively terminated by a homeostatic process that is governed by specific lipid‐derived mediators initiated by lipoxygenases. Experiments with animals and humans support a proinflammatory role for the 5‐lipoxygenase system. In contrast, results from animal experiments showa range of responses with the 12/15‐lipoxygenase pathways in atherosclerosis. To date, the only two clinical epidemiology human studies both support an antiatherogenic role for 12/15‐lipoxygenase downstream actions. We tested the hypothesis that atherosclerosis results from a failure in the resolution of local inflammation by analyzing apolipoprotein E‐deficient mice with 1 ) global leukocyte 12/15‐lipoxygenase deficiency, 2 ) normal enzyme expression, or 3 ) macrophage‐specific 12/15‐lipoxygenase overexpression. Results from these indicate that 12/15‐lipoxy‐genase expression protects mice against atherosclerosis via its role in the local biosynthesis of lipid mediators, including lipoxin A 4 , resolvin D1, and protectin D1. These mediators exert potent agonist actions on macrophages and vascular endothelial cells that can control the magnitude of the local inflammatory response. Taken together, these findings suggest that a failure of local endogenous resolution mechanisms may underlie the unremitting inflammation that fuels atherosclerosis.—Merched, A. J., Ko, K., Gotlinger, K. H., Serhan, C. N. Chan, L. Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J. 22, 3595–3606 (2008)

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Authors: Merched, A. J., Ko, K., Gotlinger, K. H., Serhan, C. N., & Chan, L.
Affiliations: Baylor St. Luke's Medical Center (US)
Brigham and Women's Hospital (US)
ORCID: Merched, Aksam J.
Serhan, Charles N.
Chan, Lawrence
Venue: The FASEB Journal
Publisher: Wiley
Published: 2008-06-17
Volume: 22
Issue: 10
Pages: 3595-3606
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.08-112201
PMC: PMC2537438
OpenAlex: W2074102438
Cited by: 414
References: 55
Citations by year: 2026: 6 · 2025: 6 · 2024: 9 · 2023: 20 · 2022: 14 · 2021: 23 · 2020: 22 · 2019: 17 · 2018: 36 · 2017: 27 · 2016: 32 · 2015: 31 · 2014: 30 · 2013: 28 · 2012: 22
FWCI: 27.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association (0465093Y, 0730172N)
National Institutes of Health (P50 DE016191, HL‐51586)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: atherosclerosis, inflammation resolution, lipid mediators, 12/15-lipoxygenase, 5-lipoxygenase, lipoxin A4, resolvin D1, protectin D1, macrophages, vascular inflammation, ApoE-deficient mice
MeSH terms: Animals, Apolipoproteins E, Arachidonate 12-Lipoxygenase, Arachidonate 15-Lipoxygenase, Docosahexaenoic Acids, Endothelium, Vascular, Humans, Interleukins, Macrophages, Vasculitis, Mice, Knockout, Lipoxins, Atherosclerosis, Mice

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Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators

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