ArticleThe Journal of biological chemistry2013
12/15-Lipoxygenase mediates high-fat diet-induced endothelial tight junction disruption and monocyte transmigration: a new role for 15(S)-hydroxyeicosatetraenoic acid in endothelial cell dysfunction.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- 12/15-lipoxygenase mediates disturbed flow-induced endothelial dysfunction and atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.Research square · 2024Article
- Requirement of Site-Specific Tyrosine Phosphorylation of Cortactin in Retinal Neovascularization and Vascular Leakage.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- N-Acetylcysteine Decreases Myocardial Content of Inflammatory Mediators Preventing the Development of Inflammation State and Oxidative Stress in Rats Subjected to a High-Fat Diet.International journal of inflammation · 2023Article
- Growth State-Dependent Expression of Arachidonate Lipoxygenases in the Human Endothelial Cell Line EA.hy926.Cells · 2022Article
- Article
- Met-RANTES preserves the blood-brain barrier through inhibiting CCR1/SRC/Rac1 pathway after intracerebral hemorrhage in mice.Fluids and barriers of the CNS · 2022Article
- The Role of 12/15-Lipoxygenase and Its Various Metabolites Generated from Multiple Polyunsaturated Fatty Acids as Substrates in Inflammatory Responses.BioMed research international · 2022Review
- Regulation of Tissue Inflammation by 12-Lipoxygenases.Biomolecules · 2021Review
- Electroacupuncture Inhibits Atherosclerosis through Regulating Intestinal Flora and Host Metabolites in Rabbit.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Driving Forces of the Bubble-Driven Tubular Micromotor Based on the Full Life-Cycle of the Bubble.Micromachines · 2019Article
- Cholesterol crystals promote endothelial cell and monocyte interactions via HRedox biology · 2019Article
- 12(S)-hydroxyeicosatetraenoic acid impairs vascular endothelial permeability by altering adherens junction phosphorylation levels and affecting the binding and dissociation of its components in high glucose-induced vascular injury.Journal of diabetes investigation · 2019Article
- Small GTPases and Their Role in Vascular Disease.International journal of molecular sciences · 2019Review
- Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.Progress in lipid research · 2019Review
- Bioactive lipids and pathological retinal angiogenesis.British journal of pharmacology · 2019Review
- Cholesterol crystals increase vascular permeability by inactivating SHP2 and disrupting adherens junctions.Free radical biology & medicine · 2018Article
- Resolvin D1 blocks HFree radical biology & medicine · 2018Article
- Expression profiles of microRNAs in oxidized low-density lipoprotein-stimulated RAW 264.7 cells.In vitro cellular & developmental biology. Animal · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A convincing body of evidence suggests that 12/15-lipoxygenase (12/15-LO) plays a role in atherosclerosis. However, the mechanisms of its involvement in the pathogenesis of this disease are not clear. Therefore, the purpose of this study is to understand the mechanisms by which 12/15-LO mediates endothelial dysfunction. 15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 12/15-LO metabolite of arachidonic acid (AA), induced endothelial barrier permeability via Src and Pyk2-dependent zonula occluden (ZO)-2 tyrosine phosphorylation and its dissociation from the tight junction complexes. 15(S)-HETE also stimulated macrophage adhesion to the endothelial monolayer in Src and Pyk2-dependent manner. Ex vivo studies revealed that exposure of arteries from WT mice to AA or 15(S)-HETE led to Src-Pyk2-dependent ZO-2 tyrosine phosphorylation, tight junction disruption, and macrophage adhesion, whereas the arteries from 12/15-LO knock-out mice are protected from these effects of AA. Feeding WT mice with a high-fat diet induced the expression of 12/15-LO in the arteries leading to tight junction disruption and macrophage adhesion and deletion of the 12/15-LO gene disallowed these effects. Thus, the findings of this study provide the first evidence of the role of 12/15-LO and its AA metabolite, 15(S)-HETE, in high-fat diet-induced endothelial tight junction disruption and macrophage adhesion, the crucial events underlying the pathogenesis of atherosclerosis.
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