ArticleProceedings of the National Academy of Sciences of the United States of America2012
Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Effect of zileuton and celecoxib on urinary LTE4 and PGE-M levels in smokers.Cancer prevention research (Philadelphia, Pa.) · 2013Trial
- The regulation of COX-2, ABCA1, and ABCG1 by the lncRNA PACERR links the inflammatory response and cholesterol homeostasis.Cell reports · 2026Article
- Concomitant COX-1 and COX-2 suppression is not sufficient to induce enteropathy associated with chronic NSAID use.The Journal of clinical investigation · 2026Article
- Depression of tryptophan may contribute to adverse effects of naproxen.Nature communications · 2026Article
- Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs.bioRxiv : the preprint server for biology · 2024Article
- Prostanoids in Cardiac and Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways.Biomedicines · 2023Article
- Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution.Nature metabolism · 2022Article
- Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- Effects of nitro-butoxyl- and butyl-esters of non-steroidal anti-inflammatory drugs compared with parent compounds on the contractility of digital arterial smooth muscle from the fallow deer (Dama dama).Inflammopharmacology · 2021Article
- New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases.Molecular medicine (Cambridge, Mass.) · 2021Review
- Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis.Cardiovascular research · 2020Article
- Bmal1 Deletion in Myeloid Cells Attenuates Atherosclerotic Lesion Development and Restrains Abdominal Aortic Aneurysm Formation in Hyperlipidemic Mice.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Tumor cell-intrinsic EPHA2 suppresses anti-tumor immunity by regulating PTGS2 (COX-2).The Journal of clinical investigation · 2019Article
- Cyclooxygenase-2, Asymmetric Dimethylarginine, and the Cardiovascular Hazard From Nonsteroidal Anti-Inflammatory Drugs.Circulation · 2018Article
- Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2.Cell reports · 2018Article
- Cold-Induced Browning of Inguinal White Adipose Tissue Is Independent of Adipose Tissue Cyclooxygenase-2.Cell reports · 2018Article
- Cardiovascular Consequences of Prostanoid I Receptor Deletion in Microsomal Prostaglandin E Synthase-1-Deficient Hyperlipidemic Mice.Circulation · 2016Article
- PGE2, Kidney Disease, and Cardiovascular Risk: Beyond Hypertension and Diabetes.Journal of the American Society of Nephrology : JASN · 2016Review
- Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival.Science translational medicine · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Suppression of cyclooxygenase 2 (COX-2)-derived prostacyclin (PGI(2)) is sufficient to explain most elements of the cardiovascular hazard from nonsteroidal antinflammatory drugs (NSAIDs). However, randomized trials are consistent with the emergence of cardiovascular risk during chronic dosing with NSAIDs. Although deletion of the PGI(2) receptor fosters atherogenesis, the importance of COX-2 during development has constrained the use of conventional knockout (KO) mice to address this question. We developed mice in which COX-2 was deleted postnatally, bypassing cardiorenal defects exhibited by conventional KOs. When crossed into ApoE-deficient hyperlipidemic mice, COX-2 deletion accelerated atherogenesis in both genders, with lesions exhibiting leukocyte infiltration and phenotypic modulation of vascular smooth muscle cells, as reflected by loss of α-smooth muscle cell actin and up-regulation of vascular cell adhesion molecule-1. Stimulated peritoneal macrophages revealed suppression of COX-2-derived prostanoids and augmented 5-lipoxygenase product formation, consistent with COX-2 substrate rediversion. Although deletion of the 5-lipoxygenase activating protein (FLAP) did not influence atherogenesis, it attenuated the proatherogeneic impact of COX-2 deletion in hyperlipidemic mice. Chronic administration of NSAIDs may increasingly confer a cardiovascular hazard on patients at low initial risk. Promotion of atherogenesis by postnatal COX-2 deletion affords a mechanistic explanation for this observation. Coincident inhibition of FLAP may offer an approach to attenuating such a risk from NSAIDs.
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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.