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

Keiichi Enjyoji, Jean Sévigny, Yuan Lin, Paul S. Frenette, Patricia D. Christie, Jan Schulte Am Esch, Masato Imai, Jay M. Edelberg, Helen Rayburn, Miroslaw Lech, David L. Beeler, Eva Csizmadia, Denisa D. Wagner, Simon C. Robson, Robert D. Rosenberg

Research output: Contribution to journalArticle

433 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1010-1017
Number of pages8
JournalNature Medicine
Volume5
Issue number9
DOIs
StatePublished - Sep 1999
Externally publishedYes

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Apyrase
Platelets
Hemostasis
Blood Platelets
Blood Vessels
Adenosine Triphosphate
Purinergic P2Y1 Receptors
Bleeding Time
Platelet Aggregation Inhibitors
Platelet Activation
Coagulation
Fibrin
Grafts
Chemical activation
Transplants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Enjyoji, K., Sévigny, J., Lin, Y., Frenette, P. S., Christie, P. D., Am Esch, J. S., ... Rosenberg, R. D. (1999). Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nature Medicine, 5(9), 1010-1017. https://doi.org/10.1038/12447

Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. / Enjyoji, Keiichi; Sévigny, Jean; Lin, Yuan; Frenette, Paul S.; Christie, Patricia D.; Am Esch, Jan Schulte; Imai, Masato; Edelberg, Jay M.; Rayburn, Helen; Lech, Miroslaw; Beeler, David L.; Csizmadia, Eva; Wagner, Denisa D.; Robson, Simon C.; Rosenberg, Robert D.

In: Nature Medicine, Vol. 5, No. 9, 09.1999, p. 1010-1017.

Research output: Contribution to journalArticle

Enjyoji, K, Sévigny, J, Lin, Y, Frenette, PS, Christie, PD, Am Esch, JS, Imai, M, Edelberg, JM, Rayburn, H, Lech, M, Beeler, DL, Csizmadia, E, Wagner, DD, Robson, SC & Rosenberg, RD 1999, 'Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation', Nature Medicine, vol. 5, no. 9, pp. 1010-1017. https://doi.org/10.1038/12447
Enjyoji, Keiichi ; Sévigny, Jean ; Lin, Yuan ; Frenette, Paul S. ; Christie, Patricia D. ; Am Esch, Jan Schulte ; Imai, Masato ; Edelberg, Jay M. ; Rayburn, Helen ; Lech, Miroslaw ; Beeler, David L. ; Csizmadia, Eva ; Wagner, Denisa D. ; Robson, Simon C. ; Rosenberg, Robert D. / Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. In: Nature Medicine. 1999 ; Vol. 5, No. 9. pp. 1010-1017.
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