Journal article
The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation
Blood, Vol.113(21), pp.5323-5329
Thrombosis and Hemostasis
05/21/2009
DOI: 10.1182/blood-2008-07-169359
PMCID: PMC2686194
PMID: 19109562
Abstract
ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor (VWF). We previously identified 2 types of mouse
Adamts13
gene: the 129/Sv-strain
Adamts13
gene encodes the long-form ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain
Adamts13
gene encodes the short-form ADAMTS13 lacking the distal C-terminal domains. To assess the physiologic significance of the distal C-terminal domains of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice (
Adamts13
S/S
) that carry the short-form ADAMTS13. Similar to wild-type 129/Sv mice (
Adamts13
L/L
),
Adamts13
S/S
did not have ultralarge VWF multimers in plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice (
Adamts13
−/−
). However, in vitro thrombogenesis under flow at a shear rate of 5000 s
−1
was accelerated in
Adamts13
S/S
compared with
Adamts13
L/L
. Both in vivo thrombus formation in ferric chloride–injured arterioles and thrombocytopenia induced by collagen plus epinephrine challenge were more dramatic in
Adamts13
S/S
than in
Adamts13
L/L
but less than in
Adamts13
−/−
. These results suggested that the C-terminally truncated ADAMTS13 exhibited decreased activity in the cleavage of VWF under high shear rate. Role of the C-terminal domains may become increasingly important under prothrombotic conditions.
Details
- Title: Subtitle
- The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation
- Creators
- Fumiaki Banno - Research Institute, National Cardiovascular Center, Suita, JapanAnil K Chauhan - Immune Disease Institute andKoichi Kokame - Research Institute, National Cardiovascular Center, Suita, JapanJin Yang - Research Institute, National Cardiovascular Center, Suita, JapanShigeki Miyata - Division of Transfusion Medicine, National Cardiovascular Center, Suita, JapanDenisa D Wagner - Immune Disease Institute andToshiyuki Miyata - Research Institute, National Cardiovascular Center, Suita, Japan
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.113(21), pp.5323-5329
- Publisher
- American Society of Hematology
- Series
- Thrombosis and Hemostasis
- DOI
- 10.1182/blood-2008-07-169359
- PMID
- 19109562
- PMCID
- PMC2686194
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 05/21/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094496602771
Metrics
19 Record Views