P2Y₁₂ regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries
J. Clin. Invest. Patrick André, et al. 112:398 doi:10.1172/JCI17864 [Go to this article.]

Figure 5
Characteristics of the in vivo thrombotic process. (a) A comparison of the time for appearance of first thrombus greater than 20 μm for all three P2Y₁₂ genotypes, WT, P2Y₁₂^+/–, and P2Y₁₂^–/–, with and without addition of either ASA, epinephrine (1, 10, or 50 μM), or epinephrine plus CT51464 (+CT). (b) P2Y₁₂^–/– thrombotic process was characterized by constant embolization of thrombi greater than 25 μm and less than 50 μm (dotted bars) between 8 and 15 minutes after injury, whereas only a few large thrombi (greater than 50 μm, black bars) embolized in both WT and P2Y₁₂^+/– mice before occlusion of the blood vessel. Intravenous injection of epinephrine accelerated the thrombotic process but did not fully restore stability. When more than 50 thrombi embolized during the 7-minute period, a value of 50 was fixed. This explains the lack of error bars for the P2Y₁₂^–/– groups treated with 1 and 10 μM epinephrine. (c) Time for occlusion of mesenteric arteries. P2Y₁₂ deficiency significantly increased (P < 0.0001) the time for occlusion. P2Y₁₂^+/– mice presented an increased time for occlusion (P < 0.01 versus WT). ASA treatment of WT mice prolonged the time for occlusion (P < 0.05). Epinephrine (50 μM) restored occlusion in P2Y₁₂^–/– mice. GP IIb-IIIa antagonism in epinephrine-treated mice prevented occlusion, but was accompanied by severe bleeding at the site of vascular surgery (n = 5–12 animals).