The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis

Anil K Chauhan; Meghan T Walsh; Guojing Zhu; David Ginsburg; Denisa D Wagner; David G Motto

doi:10.1182/blood-2007-08-108571

Back

The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis

Journal article

Open access

Peer reviewed

The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis

Anil K Chauhan, Meghan T Walsh, Guojing Zhu, David Ginsburg, Denisa D Wagner and David G Motto

Blood, Vol.111(7), pp.3452-3457

Hemostasis, Thrombosis, and Vascular Biology

04/01/2008

DOI: 10.1182/blood-2007-08-108571

PMCID: PMC2275014

PMID: 18083848

Files and links (1)

url

https://doi.org/10.1182/blood-2007-08-108571View

Published (Version of record) Open Access

Abstract

Ultralarge von Willebrand factor (UL-VWF) multimers are thought to play a central role in pathogenesis of the disease thrombotic thrombocytopenic purpura (TTP); however, experimental evidence in support of this hypothesis has been difficult to establish. Therefore, to examine directly the requirement for VWF in TTP pathogenesis, we generated ADAMTS13-deficient mice on a TTP-susceptible genetic background that were also either haploinsufficient (Vwf +/− ) or completely deficient (Vwf −/− ) in VWF. Absence of VWF resulted in complete protection from shigatoxin (Stx)–induced thrombocytopenia, demonstrating an absolute requirement for VWF in this model (Stx has been shown previously to trigger TTP in ADAMTS13-deficient mice). We next investigated the requirements for ADAMTS13 and VWF in a murine model of endotoxemia. Unlike Stx-induced TTP findings, LPS-induced thrombocytopenia and mortality were not affected by either VWF or ADAMTS13 deficiency, suggesting divergent mechanisms of thrombocytopenia between these 2 disorders. Finally, we show that VWF deficiency abrogates the ADAMTS13-deficient prothrombotic state, suggesting VWF as the only relevant ADAMTS13 substrate under these conditions. Together, these findings shed new light on the potential roles played by ADAMTS13 and VWF in TTP, endotoxemia, and normal hemostasis.

Hemostasis, Thrombosis, and Vascular Biology

Details

Title: Subtitle: The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis
Creators: Anil K Chauhan - CBR Institute for Biomedical Research, and
Meghan T Walsh - CBR Institute for Biomedical Research, and
Guojing Zhu - University of Michigan, Department of Internal Medicine, and
David Ginsburg - University of Michigan, Department of Internal Medicine, and
Denisa D Wagner - CBR Institute for Biomedical Research, and
David G Motto - Departments of Internal Medicine and Pediatrics, University of Iowa College of Medicine, Iowa City
Resource Type: Journal article
Publication Details: Blood, Vol.111(7), pp.3452-3457
Series: Hemostasis, Thrombosis, and Vascular Biology
DOI: 10.1182/blood-2007-08-108571
PMID: 18083848
PMCID: PMC2275014
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Publisher: American Society of Hematology
Language: English
Date published: 04/01/2008
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094527102771

Metrics

16 Record Views

57 Times Cited - Web of Science