Abstract | OBJECTIVE:
ADP is a key platelet agonist in thromboembolism. One of the receptors involved in ADP-induced platelet activation is the P2Y12 receptor, which is a target for antithrombotic drugs. METHODS AND RESULTS: Here, we present first evidence for a differential role of this receptor in thrombus and embolus formation in vivo. Anesthetized rabbits were treated with the selective P2Y12 antagonists AR-C69931 MX (3 microg x kg x min(-1) IV) or clopidogrel (25 mg/kg orally). Efficacy of these treatments was monitored by aggregation and thrombin generation measurements in blood samples ex vivo. Mesenteric arterioles were mechanically injured; thrombus growth and subsequent embolus formation were visualized by real-time intravital microscopy. AR-C69931 MX and clopidogrel significantly (P<0.05) reduced the total duration of embolization (by 52% and 36%, respectively), and fewer and smaller emboli were produced. The size of the initial thrombus was significantly reduced (P<0.005), but its stability was unaffected: plug formation was still effective. CONCLUSIONS:
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Authors | Miriam A van Gestel, Johan W M Heemskerk, Dick W Slaaf, Viviane V T Heijnen, Robert S Reneman, Mirjam G A oude Egbrink |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 23
Issue 3
Pg. 518-23
(Mar 01 2003)
ISSN: 1524-4636 [Electronic] United States |
PMID | 12615691
(Publication Type: Journal Article)
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Chemical References |
- Membrane Proteins
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2Y12
- Adenosine Monophosphate
- cangrelor
- Clopidogrel
- Thrombin
- Ticlopidine
- Calcium
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Topics |
- Adenosine Monophosphate
(analogs & derivatives, pharmacology)
- Administration, Oral
- Animals
- Blood Platelets
(metabolism)
- Calcium
(metabolism)
- Clopidogrel
- Female
- Male
- Membrane Proteins
- Platelet Activation
(drug effects)
- Platelet Aggregation
(drug effects)
- Purinergic P2 Receptor Antagonists
- Rabbits
- Receptors, Purinergic P2Y12
- Thrombin
(biosynthesis)
- Thromboembolism
(drug therapy, metabolism)
- Ticlopidine
(analogs & derivatives, pharmacology)
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