Arteriosclerosis, thrombosis, and vascular biology, 2010-12, Vol.30 (12), p.2385
2010
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Ticagrelor effectively and reversibly blocks murine platelet P2Y12-mediated thrombosis and demonstrates a requirement for sustained P2Y12 inhibition to prevent subsequent neointima
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2010-12, Vol.30 (12), p.2385
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Our goal was to study the effects of ticagrelor on murine platelet function and thrombosis and characterize the time course of P2Y(12) inhibition required to inhibit neointima formation following vascular injury. Mice were treated with ticagrelor or vehicle. Platelet aggregation and P-selectin expression were assessed over time, and thrombus formation was assessed in laser-injured cremasteric arterioles of P2Y(12)+/+ and P2Y(12)-/- mice. Neointima formation in FeCl(3)-injured carotid artery was assessed in C57BL/6 mice treated with different regimens of ticagrelor. Ticagrelor inhibited platelet aggregation and P-selectin expression in a dose-dependent, reversible manner. Ticagrelor inhibited thrombus formation to the same extent as seen in P2Y(12)-/- mice. Neointima formation was markedly reduced in mice treated with ticagrelor before and 4 hours after injury (neointima area: control, 39 921±22 749 μm(2), versus ticagrelor, 3705±2600 μm(2); P<0.01), whereas administration of ticagrelor either before injury only or from 4 hours postinjury was ineffective. Ticagrelor effectively and reversibly inhibits P2Y(12)-mediated platelet function and thrombosis in mice. P2Y(12) inhibition is required both at the time of and after injury to effectively inhibit neointima formation. Additional studies are warranted to evaluate the role of P2Y(12) inhibition in preventing restenosis.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1524-4636DOI: 10.1161/ATVBAHA.110.210732Titel-ID: cdi_pubmed_primary_21071697
- Format
- –
- Schlagworte
- Adenosine - analogs & derivatives, Adenosine - pharmacokinetics, Adenosine - pharmacology, Animals, Bleeding Time, Blood Coagulation - drug effects, Blood Platelets - drug effects, Blood Platelets - metabolism, Carotid Artery Injuries - metabolism, Carotid Artery Injuries - pathology, Carotid Artery Injuries - prevention & control, Carotid Artery, Common - drug effects, Carotid Artery, Common - pathology, Carotid Stenosis - metabolism, Carotid Stenosis - pathology, Carotid Stenosis - prevention & control, Cell Proliferation - drug effects, Disease Models, Animal, Dose-Response Relationship, Drug, Fibrinolytic Agents - pharmacokinetics, Fibrinolytic Agents - pharmacology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, P-Selectin - blood, Platelet Aggregation - drug effects, Platelet Aggregation Inhibitors - pharmacokinetics, Platelet Aggregation Inhibitors - pharmacology, Purinergic P2Y Receptor Antagonists - pharmacokinetics, Purinergic P2Y Receptor Antagonists - pharmacology, Receptors, Purinergic P2Y12 - deficiency, Receptors, Purinergic P2Y12 - drug effects, Receptors, Purinergic P2Y12 - genetics, Receptors, Purinergic P2Y12 - metabolism, Thrombosis - blood, Thrombosis - prevention & control, Tunica Intima - drug effects, Tunica Intima - pathology