ArticleBlood2012
NPP4 is a procoagulant enzyme on the surface of vascular endothelium.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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, 45 citations in OpenAlex.
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.Amino acids · 2024Article
- Review
- The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos.Communications biology · 2021Article
- Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds.Materials today. Bio · 2021Article
- Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy.RSC medicinal chemistry · 2021Article
- Tanshinones induce tumor cell apoptosis via directly targeting FHIT.Scientific reports · 2021Article
- Diabetes and hypertension: Pivotal involvement of purinergic signaling.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Improving the Pharmacodynamics and In Vivo Activity of ENPP1-Fc Through Protein and Glycosylation Engineering.Clinical and translational science · 2021Article
- Article
- Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination.Leukemia · 2020Article
- Crystallization of ectonucleotide phosphodiesterase/pyrophosphatase-3 and orientation of the SMB domains in the full-length ectodomain.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Increased ApPurinergic signalling · 2018Article
- Crystal structure and substrate binding mode of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3).Scientific reports · 2018Article
- The Essential Ectoenzyme SmNPP5 from the Human Intravascular Parasite Schistosoma mansoni is an ADPase and a Potent Inhibitor of Platelet Aggregation.Thrombosis and haemostasis · 2018Article
- Review
- Discovery and synthetic optimization of a novel scaffold for hydrophobic tunnel-targeted autotaxin inhibition.Bioorganic & medicinal chemistry · 2016Article
- Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase.Scientific reports · 2016Article
- ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.Nature communications · 2015Article
- Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.Molecular pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that the primary and secondary waves of aggregation and dense granule release are strongly induced by nanomolar NPP4 in a concentration-dependent manner in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors. Collectively, these studies define the biologic and enzymatic basis for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4 promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at the site of vascular injury.
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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.