Role of the CD39/CD73 purinergic pathway in modulating arterial thrombosis in mice

Covarrubias, Roman, Chepurko, Elena, Reynolds, Adam, Huttinger, Zachary M., Huttinger, Ryan, Stanfill, Katherine, Wheeler, Debra G., Novitskaya, Tatiana, Robson, Simon C., Dwyer, Karen M., Cowan, PeterJ. and Gumina, Richard J. 2016, Role of the CD39/CD73 purinergic pathway in modulating arterial thrombosis in mice, Arteriosclerosis, thrombosis, and vascular biology, vol. 36, no. 9, pp. 1809-1820, doi: 10.1161/ATVBAHA.116.307374.

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Title Role of the CD39/CD73 purinergic pathway in modulating arterial thrombosis in mice
Author(s) Covarrubias, Roman
Chepurko, Elena
Reynolds, Adam
Huttinger, Zachary M.
Huttinger, Ryan
Stanfill, Katherine
Wheeler, Debra G.
Novitskaya, Tatiana
Robson, Simon C.
Dwyer, Karen M.ORCID iD for Dwyer, Karen M.
Cowan, PeterJ.
Gumina, Richard J.
Journal name Arteriosclerosis, thrombosis, and vascular biology
Volume number 36
Issue number 9
Start page 1809
End page 1820
Total pages 24
Publisher Lippincott Williams & Wilkins
Place of publication Philadelphia, Pa.
Publication date 2016-09
ISSN 1079-5642
Summary Objective-Circulating blood cells and endothelial cells express ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine. The goal of this study was to examine the interplay between CD39 and CD73 cascade in arterial thrombosis.
Approach and Results-To determine how CD73 activity influences in vivo thrombosis, the time to ferric chloride-induced arterial thrombosis was measured in CD73-null mice. In response to 5% FeCl3, but not to 10% FeCl3, there was a significant decrease in the time to thrombosis in CD73-null mice compared with wild-Type mice. In mice overexpressing CD39, ablation of CD73 did not inhibit the prolongation in the time to thrombosis conveyed by CD39 overexpression. However, the CD73 inhibitor α-β-methylene-ADP nullified the prolongation in the time to thrombosis in human CD39 transgenic (hC39-Tg)/CD73-null mice. To determine whether hematopoietic-derived cells or endothelial cell CD39 activity regulates in vivo arterial thrombus, bone marrow transplant studies were conducted. FeCl3-induced arterial thrombosis in chimeric mice revealed a significant prolongation in the time to thrombosis in hCD39-Tg reconstituted wild-Type mice, but not on wild-Type reconstituted hCD39-Tg mice. Monocyte depletion with clodronate-loaded liposomes normalized the time to thrombosis in hCD39-Tg mice compared with hCD39-Tg mice treated with control liposomes, demonstrating that increased CD39 expression on monocytes protects against thrombosis. Conclusions-These data demonstrate that ablation of CD73 minimally effects in vivo thrombosis, but increased CD39 expression on hematopoietic-derived cells, especially monocytes, attenuates in vivo arterial thrombosis.
Language eng
DOI 10.1161/ATVBAHA.116.307374
Field of Research 110299 Cardiorespiratory Medicine and Haematology not elsewhere classified
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, American Heart Association, Inc.
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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