ArticleThe American journal of pathology2010
Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- Hepoxilin A(3) facilitates neutrophilic breach of lipoxygenase-expressing airway epithelial barriers.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- Specialized Pro-Resolving Mediators at the Ocular Surface: Biosynthesis, Mechanisms, and Therapeutic Potential.Biology · 2026Review
- Regulation of disease-associated microglia in the optic nerve by lipoxin BMolecular neurodegeneration · 2024Article
- Regulation of Diseases-Associated Microglia in the Optic Nerve by Lipoxin BbioRxiv : the preprint server for biology · 2024Article
- Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.International journal of molecular sciences · 2024Review
- Targeting Angiogenesis via Resolution of Inflammation.Cold Spring Harbor perspectives in medicine · 2023Review
- Probiotic Lactobacillus rhamnosus GG (LGG) restrains the angiogenic potential of colorectal carcinoma cells by activating a proresolving program via formyl peptide receptor 1.Molecular oncology · 2022Article
- Immune regulation of the ocular surface.Experimental eye research · 2022Review
- Piperlongumine alleviates corneal allograft rejectionFrontiers in immunology · 2022Article
- Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- A Bioinformatics Model of Human Diseases on the Basis of Differentially Expressed Genes (of Domestic Versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes.International journal of molecular sciences · 2021Article
- Toll-Like Receptor 7 Mediates Inflammation Resolution and Inhibition of Angiogenesis in Non-Small Cell Lung Cancer.Cancers · 2021Article
- The potential of lipid mediator networks as ocular surface therapeutics and biomarkers.The ocular surface · 2021Review
- Pro-Resolving Mediator Annexin A1 Regulates Intracellular CaFrontiers in immunology · 2021Article
- Meta-analysis of peptides to detect protein significance.Statistics and its interface · 2020Article
- Laquinimod Inhibits Inflammation-Induced Angiogenesis in the Cornea.Frontiers in medicine · 2020Article
- Crotoxin promotes macrophage reprogramming towards an antiangiogenic phenotype.Scientific reports · 2019Article
- Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.Progress in lipid research · 2019Review
- Tissue-specific contributions ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Dietary DHA amplifies LXAMucosal immunology · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inflammation and angiogenesis are intimately linked, and their dysregulation leads to pathological angiogenesis in human diseases. 15-lipoxygenase (15-LOX) and lipoxin A(4) receptors (ALX) constitute a LXA(4) circuit that is a key feature of inflammatory resolution. LXA(4) analogs have been shown to regulate vascular endothelial growth factor (VEGF)-A-induced angiogenic response in vitro. 15-LOX and ALX are highly expressed in the avascular and immune-privileged cornea. However, the role of this endogenous LXA(4) circuit in pathological neovascularization has not been determined. We report that suture-induced chronic injury in the cornea triggered polymorphonuclear leukocytes (PMN) infiltration, pathological neovascularization, and up-regulation of mediators of inflammatory angiogenesis, namely VEGF-A and the VEGF-3 receptor (FLT4). Up-regulation of the VEGF circuit and neovascularization correlated with selective changes in both 15-LOX (Alox15) and ALX (Fpr-rs2) expression and a temporally defined increase in basal 15-LOX activity. More importantly, genetic deletion of 15-LOX or 5-LOX, key and obligatory enzymes in the formation of LXA(4), respectively, led to exacerbated inflammatory neovascularization coincident with increased VEGF-A and FLT4 expression. Direct topical treatment with LXA(4), but not its metabolic precursor 15-hydroxyeicosatetraenoic acid, reduced expression of VEGF-A and FLT4 and inflammatory angiogenesis and rescued 15-LOX knockout mice from exacerbated angiogenesis. In summary, our findings and the prominent expression of 15-LOX and ALX in epithelial cells and macrophages place the LXA(4) circuit as an endogenous regulator of pathological angiogenesis.
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