Abstract
Background : Interaction of von Willebrand factor (vWF) and platelet glycoprotein Ib induces tyrosine phosphorylation of Syk, leading to initial activation of platelets at inflammatory sites. We examined the effect of aurintricarboxylic acid (ATA), an inhibitor of vWF-glycoprotein Ib interaction, on myocardial ischemia and reperfusion injury in mice.
Methods and Results : Coronary occlusion and reperfusion experiments were done in C57BL6 mice with or without ATA. Infarct size after 30 min of ischemia followed by 120 min of reperfusion was decreased by ATA. Phosphorylation of platelet Syk, which is coupled with GPIb, was measured after 30 min of ischemia followed by 15 min of reperfusion. Syk activity was decreased in ATA-treated mice compared with sham-operated mice. Moreover, regardless of the presence or absence of ATA, plasma vWF levels were increased after reperfusion.
Conclusions : These results indicate that the activation of platelets through vWF-GPIb intereaction plays an important role in myocardial ischemia-reperfusion injury, and that ATA is a potential agent to prevent this injury. This observation provides a rationale for focusing on antiplatelet therapy as a treatment for ischemic heart disease.
