1. Vasodilator-stimulated phosphoprotein (VASP) is not a major mediator of platelet aggregation, thrombogenesis, haemostasis, and antiplatelet effect of prasugrel in rats.
- Author
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Ito Y, Ohno K, Morikawa Y, Tomizawa A, Mizuno M, and Sugidachi A
- Subjects
- Animals, Cell Adhesion Molecules genetics, Collagen toxicity, Female, Hemostasis drug effects, Hemostasis physiology, Microfilament Proteins genetics, P-Selectin metabolism, Phosphoproteins genetics, Phosphorylation, Piperazines pharmacology, Platelet Aggregation drug effects, Platelet Aggregation physiology, Rats, Mutant Strains, Rats, Sprague-Dawley, Thrombocytopenia chemically induced, Thrombocytopenia genetics, Cell Adhesion Molecules metabolism, Microfilament Proteins metabolism, Phosphoproteins metabolism, Platelet Aggregation Inhibitors pharmacology, Prasugrel Hydrochloride pharmacology, Thrombosis genetics
- Abstract
Vasodilator-stimulated phosphoprotein (VASP) is a member of actin regulatory proteins implicated in platelet adhesion. In addition, phosphorylation of VASP is utilised for the assessment of platelet reactivity in patients treated with P2Y
12 receptor antagonists, a class of antiplatelet agents. However, the role of VASP in platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of P2Y12 receptor antagonists remains unclear. We investigated these effects using heterozygous and homozygous VASP knockout rats generated with a CRISPR/Cas9 system. Baseline characteristics, such as haematology and other biochemical parameters, were comparable among the genotypes. In vitro platelet aggregation stimulated by adenosine diphosphate (ADP) or collagen, P-selectin expression of rat platelets treated with ADP, and in vivo thrombocytopenia induced by collagen were also comparable among the genotypes. In addition, in vivo thrombogenesis in a ferric chloride-induced arterial thrombosis model and bleeding time were also comparable among the genotypes. Furthermore, the in vitro antiplatelet effect of prasugrel, a third-generation P2Y12 receptor antagonist, was unaffected by VASP knockout. Although phosphorylated VASP is still an important surrogate marker specific for P2Y12 antagonists, our findings demonstrate that VASP is not a major mediator of platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of prasugrel in rats. more...- Published
- 2018
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