ArticleBlood2015
The ABCC4 membrane transporter modulates platelet aggregation.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The Role of Cilostazol, a Phosphodiesterase-3 Inhibitor, in the Development of Atherosclerosis and Vascular Biology: A Review with Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Integrated SNP and SV Analyses Reveal Genetic Mechanisms Underlying High-Altitude Adaptation in Goats.Animals : an open access journal from MDPI · 2026Article
- Article
- ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Structural insights into human ABCC4-mediated transport of platelet agonist and antagonist.Nature cardiovascular research · 2023Article
- Insights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter.Nature cardiovascular research · 2023Article
- The human ATP-binding cassette (ABC) transporter superfamily.Human mutation · 2022Review
- Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.Haematologica · 2022Article
- Cilostazol: a Review of Basic Mechanisms and Clinical Uses.Cardiovascular drugs and therapy · 2022Review
- Article
- MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation.Journal of thrombosis and thrombolysis · 2021Article
- Multidrug resistance-associated protein 4 (Mrp4) is a novel genetic factor in the pathogenesis of obesity and diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Lack of Multidrug Resistance-associated Protein 4 Prolongs Partial Hepatectomy-induced Hepatic Steatosis.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Article
- Article
- Lack of multidrug resistance-associated protein 4 (Mrp4) alters the kinetics of acetaminophen toxicity.Toxicology reports · 2019Article
- MiR-21 role in aspirin-dependent PPARα and multidrug resistance protein 4 upregulation.Research and practice in thrombosis and haemostasis · 2018Article
- Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.JACC. Basic to translational science · 2018Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- ABC Transport Proteins in Cardiovascular Disease-A Brief Summary.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Controlling the activation of platelets is a key strategy to mitigate cardiovascular disease. Previous studies have suggested that the ATP-binding cassette (ABC) transporter, ABCC4, functions in platelet-dense granules. Using plasma membrane biotinylation and super-resolution microscopy, we demonstrate that ABCC4 is primarily expressed on the plasma membrane of both mouse and human platelets. Platelets lacking ABCC4 have unchanged dense-granule function, number, and volume, but harbor a selective impairment in collagen-induced aggregation. Accordingly, Abcc4 knockout (KO) platelet attachment to a collagen substratum was also faulty and associated with elevated intracellular cyclic AMP (cAMP) and reduced plasma membrane localization of the major collagen receptor, GPVI. In the ferric-chloride vasculature injury model, Abcc4 KO mice exhibited markedly impaired thrombus formation. The attenuation of platelet aggregation by the phosphodiesterase inhibitor EHNA (a non-ABCC4 substrate), when combined with Abcc4 deficiency, illustrated a crucial functional interaction between phosphodiesterases and ABCC4. This was extended in vivo where EHNA dramatically prolonged the bleeding time, but only in Abcc4 KO mice. Further, we demonstrated in human platelets that ABCC4 inhibition, when coupled with phosphodiesterase inhibition, strongly impaired platelet aggregation. These findings have important clinical implications because they directly highlight an important relationship between ABCC4 transporter function and phosphodiesterases in accounting for the cAMP-directed activity of antithrombotic agents.
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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.