Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation

K Enjyoji, J Sévigny, Y Lin, PS Frenette, PD Christie… - Nature medicine, 1999 - nature.com
K Enjyoji, J Sévigny, Y Lin, PS Frenette, PD Christie, JSA Esch, M Imai, JM Edelberg
Nature medicine, 1999nature.com
CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an
important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged
bleeding times with minimally perturbed coagulation parameters. Platelet interactions with
injured mesenteric vasculature were considerably reduced in vivo and purified mutant
platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was
reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping …
Abstract
CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions.
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