The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E–deficient mice
Open accessAbstract
Atherosclerosis may be viewed as an inflammatory disease process that includes early oxidative modification of LDLs, leading to foam cell formation. This "oxidation hypothesis" has gained general acceptance in recent years, and evidence for the role of lipoxygenases in initiation of, or participation in, the oxidative process is accumulating. However, the relative contribution of macrophage-expressed lipoxygenases to atherogenesis in vivo remains unknown. Here, we provide in vivo evidence for the role of 12/15-lipoxygenase in atherogenesis and demonstrate diminished plasma IgG autoantibodies to oxidized LDL epitopes in 12/15-lipoxygenase knockout mice crossbred with atherosclerosis-prone apo E-deficient mice (apo E-/-/L-12LO-/-). In chow-fed 15-week-old apo E-/-/L-12LO-/- mice, the extent of lesions in whole-aorta en face preparations (198 +/- 60 microm2) was strongly reduced (P < 0.001, n = 12) when compared with 12/15-lipoxygenase-expressing controls (apo E-/-/L-12LO+/+), which showed areas of lipid deposition (15,700 +/- 2,688 microm2) in the lesser curvature of the aortic arch, branch points, and in the abdominal aorta. These results were observed despite cholesterol, triglyceride, and lipoprotein levels that were similar to those in apo E-deficient mice. Evidence for reduced lesion development was observed even at 1 year of age in apo E-/-/L-12LO-/- mice. The combined data indicate a role for 12/15-lipoxygenase in the pathogenesis of atherosclerosis and suggest that inhibition of this enzyme may decrease disease progression.
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“Several lipoxygenases have been related to inflammation and cardiovascular disease, in particular, 5-lipoxygenase and 12/15-lipoxygenase (203, 597, 636).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [203]
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Lusis, A. J. (2000) · Nature · doi:10.1038/35025203 · Cited by 4,880
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Oxidative Stress and Vascular Disease
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Metadata
- Authors
- Cyrus, T., Witztum, J. L., Rader, D. J., Tangirala, R., Fazio, S., Linton, M. F., & Funk, C. D.
- Affiliations
- University of Pennsylvania (US)
- University of California San Diego (US)
- Vanderbilt University (US)
- Corresponding author
- Funk, Colin D.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-06-01
- Volume
- 103
- Issue
- 11
- Pages
- 1597-1604
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408369
- OpenAlex
- W2149303684
- Cited by
- 523
- References
- 63
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 17 · 2015: 18 · 2014: 19 · 2013: 19 · 2012: 20
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM 15431)
- National Heart, Lung, and Blood Institute (R01HL053558, R01HL059694, HL59694, HL-53558)
- National Institute of General Medical Sciences (GM 15431, P50GM015431, P01GM015431)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- 12/15-lipoxygenase, atherosclerosis, oxidized LDL, IgG autoantibodies, macrophages, foam cell formation, LDL oxidation, aortic lesions, atherogenesis
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Arachidonate 12-Lipoxygenase, Arachidonate 15-Lipoxygenase, Arteriosclerosis, Autoantibodies, Female, Lipoproteins, LDL, Male, Mice, Inbred C57BL, Mice, Knockout, Lipid Metabolism, Mice
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