ArticleThe Journal of clinical investigation1999
Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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Who cites it
154 citing papers in PubMed, 520 citations in OpenAlex.
- Alox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity.The Journal of experimental medicine · 2026Article
- Interleukin-6 stimulates platelet 12-lipoxygenase to drive coagulation in inflammatory arthritis.Journal of lipid research · 2026Article
- Structural Improvement of the Allosteric ALOX15 Inhibitor Octyl (Molecules (Basel, Switzerland) · 2026Article
- Reactivity of mammalian lipoxygenases (ALOX isoforms) with phospholipids, biomembranes and lipoproteins.Communications biology · 2026Article
- 12/15-lipoxygenase orchestrates murine wound healing via PPARγ-activating oxylipins acting holistically to dampen inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 12/15-lipoxygenase mediates disturbed flow-induced endothelial dysfunction and atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Functional humanization of 15-lipoxygenase-1 (Alox15) protects mice from dextran sodium sulfate induced intestinal inflammation.Cellular & molecular biology letters · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- The Role of Lipids in Atherosclerosis: Focus on Molecular Biology Mechanisms and Therapeutic Approaches.Current medicinal chemistry · 2025Review
- Regulation of nitric oxide generation and consumption.International journal of biological sciences · 2025Review
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- Genetic deletion of 12/15 lipoxygenase delays vascular remodeling and limits cardiorenal dysfunction after pressure overload.Journal of molecular and cellular cardiology plus · 2023Article
- Transgenic mice overexpressing human ALOX15 under the control of the aP2 promoter are partly protected in the complete Freund's adjuvant-induced paw inflammation model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Different Structures-Similar Effect: Do Substituted 5-(4-Methoxyphenyl)-1Molecules (Basel, Switzerland) · 2023Article
- Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.Pharmacology & therapeutics · 2023Review
- Functional Characterization of Transgenic Mice Overexpressing Human 15-Lipoxygenase-1 (ALOX15) under the Control of the aP2 Promoter.International journal of molecular sciences · 2023Article
- Ferroptosis: A potential target of macrophages in plaque vulnerability.Open life sciences · 2023Review
- Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.Environmental research · 2022Article
- Myeloid LXR (Liver X Receptor) Deficiency Induces Inflammatory Gene Expression in Foamy Macrophages and Accelerates Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
94 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.