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Blood, 30 July 2009, Vol. 114, No. 5, pp. 1083-1090. Prepublished online as a Blood First Edition Paper on April 24, 2009; DOI 10.1182/blood-2009-03-210211. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2009-03-210211v1 114/5/1083    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Graham, G. J. Articles by Flaumenhaft, R. PubMed PubMed Citation Articles by Graham, G. J. Articles by Flaumenhaft, R. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Endobrevin/VAMP-8–dependent dense granule release mediates thrombus formation in vivo Gwenda J. Graham1, Qiansheng Ren2, James R. Dilks1, Price Blair1, Sidney W. Whiteheart2, and Robert Flaumenhaft1 1 Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; and 2 Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington Individuals whose platelets lack dense or -granules suffer various degrees of abnormal bleeding, implying that granule cargo contributes to hemostasis. Despite these clinical observations, little is known regarding the effects of impaired platelet granule secretion on thrombus formation in vivo. In platelets, SNARE proteins mediate the membrane fusion events required for granule cargo release. Endobrevin/VAMP-8 is the primary vesicle-SNARE (v-SNARE) responsible for efficient release of dense and -granule contents; thus, VAMP-8–/– mice are a useful model to evaluate the importance of platelet granule secretion in thrombus formation. Thrombus formation, after laser-induced vascular injury, in these mice is delayed and decreased, but not absent. In contrast, thrombus formation is almost completely abolished in the mouse model of Hermansky-Pudlak syndrome, ruby-eye, which lacks dense granules. Evaluation of aggregation of VAMP-8–/– and ruby-eye platelets indicates that defective ADP release is the primary abnormality leading to impaired aggregation. These results demonstrate the importance of dense granule release even in the earliest phases of thrombus formation and validate the distal platelet secretory machinery as a potential target for antiplatelet therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Granules and thrombus formation Walter H. A. Kahr Blood 2009 114: 932-933. [Abstract] [Full Text] [PDF] This article has been cited by other articles: W. H. A. Kahr Granules and thrombus formation Blood, July 30, 2009; 114(5): 932 - 933. [Abstract] [Full Text] [PDF]

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