ArticleCell metabolism2008
Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis.
Article in Cell metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 112 citations in OpenAlex.
- From Vascular Dysfunction to Atherothrombosis: The Pivotal Role of Eicosanoids and Their Receptors in Platelet and Endothelial Imbalance: A Scoping Review.International journal of molecular sciences · 2025Article
- Article
- Targeting the E Prostanoid Receptor EP4 Mitigates Cardiac Fibrosis Induced by β-Adrenergic Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Growth Hormone Alleviates Atherosclerosis Through Regulating the Activity of PI3K/AKT Pathway: Insights From Single-Cell Sequence and Mechanism Exploration.International journal of genomics · 2025Article
- Disruption of the PGEbioRxiv : the preprint server for biology · 2024Article
- Prostanoids in Cardiac and Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Peritoneal fibrosis: from pathophysiological mechanism to medicine.Frontiers in physiology · 2024Review
- Single hormone or synthetic agonist induces GProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Prostaglandin PGE2 Receptor EP4 Regulates Microglial Phagocytosis and Increases Susceptibility to Diet-Induced Obesity.Diabetes · 2023Article
- Magnetic resonance imaging contrast-enhancement with superparamagnetic iron oxide nanoparticles amplifies macrophage foam cell apoptosis in human and murine atherosclerosis.Cardiovascular research · 2023Article
- The diverse roles of macrophages in metabolic inflammation and its resolution.Frontiers in cell and developmental biology · 2023Review
- LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8.Nature cell biology · 2022Article
- Genetically personalised organ-specific metabolic models in health and disease.Nature communications · 2022Article
- AKT Isoforms in Macrophage Activation, Polarization, and Survival.Current topics in microbiology and immunology · 2022Article
- Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Review
- Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids.International journal of molecular sciences · 2021Review
- Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.eLife · 2021Article
- Platelet-conditioned media induces an anti-inflammatory macrophage phenotype through EP4.Journal of thrombosis and haemostasis : JTH · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Prostaglandin (PG) E(2), a major product of activated macrophages, has been implicated in atherosclerosis and plaque rupture. The PGE(2) receptors, EP2 and EP4, are expressed in atherosclerotic lesions and are known to inhibit apoptosis in cancer cells. To examine the roles of macrophage EP4 and EP2 in apoptosis and early atherosclerosis, fetal liver cell transplantation was used to generate LDLR(-/-) mice chimeric for EP2(-/-) or EP4(-/-) hematopoietic cells. After 8 weeks on a Western diet, EP4(-/-) --> LDLR(-/-) mice, but not EP2(-/-) --> LDLR(-/-) mice, had significantly reduced aortic atherosclerosis with increased apoptotic cells in the lesions. EP4(-/-) peritoneal macrophages had increased sensitivity to proapoptotic stimuli, including palmitic acid and free cholesterol loading, which was accompanied by suppression of activity of p-Akt, p-Bad, and NF-kappaB-regulated genes. Thus, EP4 deficiency inhibits the PI3K/Akt and NF-kappaB pathways compromising macrophage survival and suppressing early atherosclerosis, identifying macrophage EP4-signaling pathways as molecular targets for modulating the development of atherosclerosis.
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.