ArticlePloS one2013
LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04765644 (Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment), which is not on this map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment (ASCENT)
Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- In Patients Experiencing Pain and Inflammation, the Use of Non-Steroidal Anti-Inflammatory Drugs Is More Likely a Marker of the Observed Cardiovascular Risk Rather than Its Cause: A Viewpoint.Pharmacy (Basel, Switzerland) · 2026Review
- Is there a link between non-steroidal anti-inflammatory drugs and cardiovascular risk in patients with inflammatory arthritis?Atherosclerosis plus · 2026Review
- Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man.Kidney international reports · 2023Article
- Chemoinformatics approach to design and develop vanillin analogs as COX-1 inhibitor.Journal of public health in Africa · 2023Article
- New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases.Molecular medicine (Cambridge, Mass.) · 2021Review
- Role of 2‑series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non‑alcoholic fatty liver disease (Review).International journal of molecular medicine · 2021Review
- Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation.Science advances · 2021Article
- Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis.Cardiovascular research · 2020Article
- Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective.Biochemical pharmacology · 2020Review
- Peripheral-to-central immune communication at the area postrema glial-barrier following bleomycin-induced sterile lung injury in adult rats.Brain, behavior, and immunity · 2020Article
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
- Cell-Specific Gene Deletion Reveals the Antithrombotic Function of COX1 and Explains the Vascular COX1/Prostacyclin Paradox.Circulation research · 2019Article
- Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system.British journal of pharmacology · 2019Review
- Postnatal changes in constitutive cyclooxygenase‑2 expression in the mice hippocampus and its function in synaptic plasticity.Molecular medicine reports · 2019Article
- High-Throughput Screening of Lipidomic Adaptations in Cultured Cells.Biomolecules · 2019Article
- Effect of selected non-steroidal anti-inflammatory drugs on activation-induced CD25 expression on murine CD4Central-European journal of immunology · 2019Article
- Imaging of Tissue-Specific and Temporal Activation of GPCR Signaling Using DREADD Knock-In Mice.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders.Frontiers in psychiatry · 2019Review
- Letter by Mitchell et al Regarding Article, "Urinary Prostaglandin Metabolites: An Incomplete Reckoning and a Flush to Judgment".Circulation research · 2018Article
- Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase ACirculation research · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
There are two schools of thought regarding the cyclooxygenase (COX) isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.
Indexed as
Identifiers
What OpenQuestion holds
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.