Trial reportThe Journal of clinical investigation2012
Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.
Trial report in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01275300. Cited by 27 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.
A Pilot Study to Measure Plasma and Urinary Prostaglandin D2 Metabolites Evoked by Niacin
Open the trial in the graphWho cites it
27 citing papers in PubMed, 67 citations in OpenAlex.
- Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Trial
- Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.Journal of the American Heart Association · 2015Trial
- Regulatory roles of bioactive lipids in vascular homeostasis and remodeling.Medical review (2021) · 2026Review
- Prostanoids in Cardiac and Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Orthosteric and allosteric modulation of human HCAR2 signaling complex.Nature communications · 2023Article
- Association between Vitamin Intake and Chronic Kidney Disease According to a Variant Located Upstream of theNutrients · 2022Article
- Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation.Clinical science (London, England : 1979) · 2022Article
- Regulatory Roles of Phospholipase AFrontiers in immunology · 2022Review
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- 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
- DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells.Circulation · 2020Article
- Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.The Journal of pharmacology and experimental therapeutics · 2018Article
- Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting.Cellular and molecular life sciences : CMLS · 2017Review
- The expansive role of oxylipins on platelet biology.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin DThe Journal of pharmacology and experimental therapeutics · 2017Article
- High-density Lipoprotein and Low-density Lipoprotein Therapeutic Approaches in Acute Coronary Syndromes.Current cardiology reviews · 2017Review
- Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets.Frontiers in medicine · 2017Review
- Aspirin-exacerbated respiratory disease: Prevalence, diagnosis, treatment, and considerations for the future.American journal of rhinology & allergy · 2016Review
- Understanding the role of prostaglandin E2 in regulating human platelet activity in health and disease.Thrombosis research · 2015Review
- Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?Current atherosclerosis reports · 2015Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD₂ receptor DP1. NSAID-mediated suppression of COX-2-derived PGI₂ has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD₂. Here, we show that PGD₂ biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD₂ was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD₂, like PGI₂, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy.
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What Socratic 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 Socratic graph.