ArticleProceedings of the National Academy of Sciences of the United States of America2010
Increased expression of leukotriene C4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- No association of chronic obstructive pulmonary disease with abdominal aortic aneurysm growth.Heart and vessels · 2016Pooled it
- Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture.Arteriosclerosis, thrombosis, and vascular biology · 2016Trial
- Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega-3 fatty acids.Molecular nutrition & food research · 2013Trial
- Regulatory roles of bioactive lipids in vascular homeostasis and remodeling.Medical review (2021) · 2026Review
- Lipidomic insights on abdominal aortic aneurysm and peripheral arterial disease.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Histamine and TH2 cytokines regulate the biosynthesis of cysteinyl-leukotrienes and expression of their receptors in human mast cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Montelukast inhibits abdominal aortic aneurysm formation in mice via activating the AMPK/mTOR signalling pathway.Langenbeck's archives of surgery · 2024Article
- Cysteine Leukotriene Receptor Antagonist-Montelukast-Treatment Improves Experimental Abdominal Aortic Aneurysms in Mice.Cardiovascular therapeutics · 2024Article
- Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis.Biological research · 2023Article
- Early and Sustained Increases in Leukotriene BNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Montelukast Use Decreases Cardiovascular Events in Asthmatics.Frontiers in pharmacology · 2020Article
- Montelukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Induces M2 Macrophage Polarization and Inhibits Murine Aortic Aneurysm Formation.BioMed research international · 2019Article
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Bidirectional Mast Cell-Eosinophil Interactions in Inflammatory Disorders and Cancer.Frontiers in medicine · 2017Review
- Platelet-driven leukotriene C4-mediated airway inflammation in mice is aspirin-sensitive and depends on T prostanoid receptors.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Leukotriene-C4 synthase, a critical enzyme in the activation of store-independent Orai1/Orai3 channels, is required for neointimal hyperplasia.The Journal of biological chemistry · 2015Article
- 5-Lipoxygenase pathway in experimental abdominal aortic aneurysms.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Structure and inhibition of mouse leukotriene C4 synthase.PloS one · 2014Article
- Mast cells: from lipid droplets to lipid mediators.Clinical science (London, England : 1979) · 2013Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC(4), LTD(4), and LTE(4) are important mediators of asthma, and LTB(4) has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC(4) synthase (LTC(4)S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme responsible for the biosynthesis of LTB(4), are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC(4)S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB(4). Furthermore, challenge of AAA wall tissue with exogenous LTD(4) increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC(4)S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA.
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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.