2011 Fiscal Year Final Research Report
Anti-inflammatory and anti-coagulant function of ADAMTS13 expressed under blood flow
| Project/Area Number |
21592313
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Emergency medicine
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
NISHIO Kenji 奈良県立医科大学, 医学部, 准教授 (60254489)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Keywords | VWF / ADAMTS13 |
|---|
| Research Abstract |
The function of von Willebrand factor(VWF) is essential for normal hemostasis and regulated by ADAMTS13 which cleaves VWF to smaller less-active forms. We recently found that ADAMTS13 limits thrombus growth at the on-going thrombus generation process, leading speculation that the excessive function of VWF mediated by ADAMTS dysfunction may link to arterial thrombosis in the microcirculation in many diseases.
We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion(MCAO) model in Adamts13-/-and wild-type mice. After reperfusion, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13-/-mice compared to wild-type mice, which also resulted in a larger infarct volume for Adamts13-/-. Furthermore, brain ischemia induced more prominent activation of inflammatory cells co-expressing high-mobility group box1(HMGB1) and myeloperoxidase(MPO) in the cortical ischemic penumbra of Adamts13-/-mice. Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia and inflammation by regulating VWF-platelet interactions after reperfusion.
Moreover, a recombinant human ADAMTS13 infused to wild type mice before 4 hours' occlusion significantly reduced infarct volume without cerebral bleeding complications. These results indicate that ADAMTS13 could be an anti-inflammatory and anti-coagulant agent for prevention or treatment for many diseases, especially for stroke.
|
-
[Journal Article] ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury2012
Author(s)
Masayuki Fujioka, Takafumi Nakano, Kazuhide Hayakawa, Keiichi Irie, Yoshiharu Akitake, Yuya Sakamoto, Kenichi Mishima, Carl Muroi, Yasuhiro Yonekawa, Fumiaki Banno, Koichi Kokame, Toshiyuki Miyata, Kenji Nishio, Kazuo Okuchi, Katsunori Iwasaki, Michihiro
-
Journal Title
DOI
Peer Reviewed
-
-
-
[Journal Article] ADAMTS13 gene deletion aggravates ischemic brain damage : a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion2010
Author(s)
Fujioka M, Hayakawa K, Mishima K, Kunizawa A, Irie K, Higuchi S, Nakano T, Muroi C, Fukushima H, Sugimoto M, Banno F, Kokame K, Miyata T, Fujiwara M, Okuchi K, and Nishio K
-
Journal Title
Blood
Volume: 115
Pages: 1650-1653
Peer Reviewed
-
-
[Presentation] PROTECTIVE PROPERTY OF ADAMTS13 IN A MOUSE-MODEL OF ISCHEMIC STROKE XXII2009
Author(s)
K. Nishio, M. Fujioka, K. Hayakawa, K. Mishima, M. Fujiwara, F. Banno, K. Kokame, T. Miyata, Y. Shida, M. Sugimoto, T. Ueyama, H. Fukushima, K. Okuchi
Organizer
Congress of The International Society on Thrombosis and Haemostasis
Place of Presentation
Boston
Year and Date
20090711-16
-
-
