Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist.
Previous studies in experimental models revealed a role for the P2Y1 platelet ADP receptor in systemic vascular thromboembolism models. In the present work, we used models of localized arterial and venous thrombosis to assess the role of the P2Y1 receptor in these processes. Arterial thrombosis was induced in one mesenteric arteriole of a mouse using FeCl3, while venous thrombosis was studied in a Wessler model adapted to rats. P2Y1-deficient mice and mice treated with the P2Y1 antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls. Combination of P2Y1 deficiency with P2Y12 inhibition led to a significant additive effect. Venous thrombosis was slightly but significantly inhibited in MRS2179-treated rats. These results demonstrate a role for the P2Y1 receptor in both arterial and venous thrombosis, further establishing this receptor as a potential target for antithrombotic drugs.
Lenain
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Institut National de la Santé et de la Recherche Médicale (INSERM) U.311, Etablissement Français du Sang, Alsace (EFS-Alsace), 10 rue Spielmann, BP no. 36, 67065 Strasbourg Cédex, France.
Freund
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M
Léon
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Cazenave
J-P
JP
Gachet
C
C
D000244:Adenosine Diphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000077144:Clopidogrel; D004195:Disease Models, Animal; D004347:Drug Interactions; D008638:Mesenteric Arteries; D051379:Mice; D008817:Mice, Mutant Strains; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D013925:Thromboplastin / Q000008:administration & dosage / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014682:Vena Cava, Inferior
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546383:P2ry1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D013925:Thromboplastin; D000077144:Clopidogrel; D013988:Ticlopidine