ArticlePloS one2014
COX-2 protects against atherosclerosis independently of local vascular prostacyclin: identification of COX-2 associated pathways implicate Rgl1 and lymphocyte networks.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Trial
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- [RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assemblyNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Article
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- Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways.Biomedicines · 2023Article
- Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.Frontiers in physiology · 2023Review
- 3D chromatin structure in chondrocytes identifies putative osteoarthritis risk genes.Genetics · 2022Article
- Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution.Nature metabolism · 2022Article
- Systems Approach to Integrating Preclinical Apolipoprotein E-Knockout Investigations Reveals Novel Etiologic Pathways and Master Atherosclerosis Network in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases.Molecular medicine (Cambridge, Mass.) · 2021Review
- Cyclooxygenase-2 Glycosylation Is Affected by Peroxynitrite in Endothelial Cells: Impact on Enzyme Activity and Degradation.Antioxidants (Basel, Switzerland) · 2021Article
- Effects of selenium intake on the expression of prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2) and matrix metallopeptidase-9 genes in the coronary artery disease: Selenegene study, a double-blind randomized controlled trial.ARYA atherosclerosis · 2021Article
- 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
- Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis.Journal of clinical medicine · 2020Review
- Functional and structural changes in aorta of mice divergently selected for basal metabolic rate.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2020Article
- Epitranscriptomic N4-Acetylcytidine Profiling in CD4Frontiers in cell and developmental biology · 2020Article
- Cell-Specific Gene Deletion Reveals the Antithrombotic Function of COX1 and Explains the Vascular COX1/Prostacyclin Paradox.Circulation research · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE(-/-)/COX-2(-/-) mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE(-/-)/COX-2(-/-) mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs.
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Registered trials
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