ArticleJournal of thrombosis and haemostasis : JTH2012
Increased platelet activation and thrombosis in transgenic mice expressing constitutively active P2Y12.
Article in Journal of thrombosis and haemostasis : JTH, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Platelet P2YBMC biology · 2023Article
- Dysregulation in the Expression of Platelet Surface Receptors in Acute Coronary Syndrome Patients-Emphasis on P2Y12.Biology · 2022Article
- Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats.Chinese journal of integrative medicine · 2021Article
- The role of Sphingomyelin synthase 2 (SMS2) in platelet activation and its clinical significance.Thrombosis journal · 2021Article
- Imaging Platelet Processes and Function-Current and Emerging Approaches for ImagingFrontiers in immunology · 2020Review
- ASK1 facilitates tumor metastasis through phosphorylation of an ADP receptor P2YCell death and differentiation · 2017Article
- Article
- Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel.Journal of visualized experiments : JoVE · 2015Article
- Nucleotide-binding oligomerization domain 2 receptor is expressed in platelets and enhances platelet activation and thrombosis.Circulation · 2015Article
- Platelet specific promoters are insufficient to express protease activated receptor 1 (PAR1) transgene in mouse platelets.PloS one · 2014Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn our previous in vitro study, we reported a constitutively active chimeric P2Y(12) (cP2Y(12)) and found that AR-C78511 is a potent inverse agonist at this receptor. The role of cP2Y(12) in platelet activation and thrombosis is not clear.
objectivesTo investigate the physiologic implications of cP2Y(12) for platelet activation and thrombus formation, and to evaluate the antiplatelet activity of AR-C78511 as an inverse agonist. METHODS AND
resultsWe generated transgenic mice conditionally and platelet-specifically expressing cP2Y(12). High-level expression of cP2Y(12) in platelets increased platelet reactivity, as shown by increased platelet aggregation in response to multiple platelet agonists. Moreover, transgenic mice showed a shortened bleeding time, and more rapid and stable thrombus formation in mesenteric artery injured with FeCl(3). The constitutive activity of cP2Y(12) in platelets was confirmed by decreased platelet cAMP levels and constitutive Akt phosphorylation in the absence of agonists. AR-C78511 reversed the cAMP decrease in transgenic mouse platelets, and exhibited a superior antiplatelet effect to that of AR-C69931MX in transgenic mice.
conclusionsThese findings further emphasize the importance of P2Y(12) in platelet activation, hemostasis, and thrombosis, as well as the prothrombotic role of the constitutive activity of P2Y(12). Our data also validate the in vivo inverse agonist activity of AR-C78511, and confirm its superior antiplatelet activity over neutral antagonists.
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