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 P2Y(1) 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 P2Y(1) receptor in these processes. Arterial thrombosis was induced in one mesenteric arteriole of a mouse using FeCl3, while venous thrombosis was studied in a Wessier model adapted to rats. P2Y(1)-deficient mice and mice treated with the P2Y(1) antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls. Combination of P2Y(1) deficiency with P2Y(12) 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 P2Y(1) receptor in both arterial and venous thrombosis, further establishing this receptor as a potential target for antithrombotic drugs.