ArticleCardiovascular research2020
Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis.
Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
10 citing papers in PubMed, 26 citations in OpenAlex.
- A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.Rheumatology (Oxford, England) · 2025Trial
- Prostaglandins: Key players in immunomodulation of the nervous system.Neural regeneration research · 2026Article
- Photoswitchable COX-2-Selective Inhibitors as Light-Regulated Anti-Inflammatory Agents.Journal of the American Chemical Society · 2026Article
- Arzanol: A Review of Chemical Properties and Biological Activities.Plants (Basel, Switzerland) · 2025Review
- Review
- A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model.Scientific reports · 2024Article
- Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.Journal of the American Heart Association · 2024Article
- Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man.Kidney international reports · 2023Article
- Latest progress in the development of cyclooxygenase-2 pathway inhibitors targeting microsomal prostaglandin EFuture medicinal chemistry · 2022Article
- Profiling the eicosanoid networks that underlie the anti- and pro-thrombotic effects of aspirin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 8 countries.
Funding
Abstract
aimsCardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here, we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. METHODS AND
resultsInhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalization of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors.
conclusionThese data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA.
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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.