Altered response to mechanical stress and aortic aneurysm development
| Project/Area Number |
17H04289
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cardiovascular surgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Yanagisawa Hiromi 筑波大学, 生存ダイナミクス研究センター, 教授 (40746301)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | 大動脈瘤 / 大動脈解離 / メカニカルストレス / 細胞外マトリクス / 血管平滑筋細胞 / 弾性線維 / 膠原線維 / アクチン線維 / マトリセルラータンパク質 / 血管平滑筋細胞’ / フィブリン４ / シグナル伝達 / アクチン / メカノセンサー / マトリセルラータンパク / 大血管外科学 / 分子生物学 / マウスモデル |
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| Outline of Final Research Achievements |
The applicants (1) identified the mechanical stress response factor TSP1 and (2) proved its causal relationship with aortic aneurysm using a mouse model. From the analysis of human aortic aneurysm samples, we found that (3) TSP1 was significantly elevated in human thoracic aorta. These results have led to numerous publications and conference presentations. The importance of TSP1 was also found not only in aortic aneurysms but also in vascular remodeling by shunting (joint research with Emory University, USA). The relationship between vascular biomechanics and aortic aneurysms was also developed into an international collaborative study using 10 different mouse models, including 4 universities in the U.S., and we were able to achieve results beyond our expectations. For this reason, we submitted an application one year ahead.
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| Academic Significance and Societal Importance of the Research Achievements |
大動脈瘤は無症状に経過することが多く、瘤の破裂や断裂がおきると死に至る大変危険な血管の病気です。なぜこのような異常が大動脈におこるのか、その原因は完全にはわかっていません。また、発症を防ぐための予防法や、瘤の増大を止める治療法はまだ確立されていません。そこで、私たちの研究グループは、どのようにして大動脈に瘤が発症するかということを研究しました。その結果、トロンボスポンディンという細胞から分泌されるタンパク質が瘤の病変で増加しており、さまざまな細胞内のシグナル経路を誘導することがわかりました。今後さらに、トロンボスポンディンの発現を制御する分子や、瘤形成のメカニズムを研究する予定です。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Fibulin-4 deficiency differentially affects cytoskeleton structure and dynamics as well as TGFβ signaling.2019
Author(s)
J. Burger, N. van Vliet, P. van Heijningen, H. Kumra, G. J. Kremers, M. Alves, G. van Cappellen, H. Yanagisawa, D. P. Reinhardt, R. Kanaar, I. van der Pluijm, J. Essers
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Journal Title
Cell Signaling
Volume: 58
Pages: 65-78
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Role of thrombospondin-1 in mechanotransduction and development of thoracic aortic aneurysm in mouse and humans.2018
Author(s)
Yamashiro Y, Thang BQ, Shin SJ, Lino CA, Nakamura T, Kim J, Sugiyama K, Tokunaga C, Sakamoto H, Osaka M, Davis EC, Wagenseil JE, Hiramatsu Y and Yanagisawa H.
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Journal Title
Circulation Research
Volume: 123(6)
Issue: 6
Pages: 660-672
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1.2017
Author(s)
Kim CW, Pokutta-Paskaleva A, Kumar S, Timmins LH, Morris AD, Kang DW, Dalal S, Chadid T, Kuo KM, Raykin J, Li H, Yanagisawa H, Gleason RL Jr, Jo H, Brewster LP.
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Journal Title
Circulation
Volume: 136(13)
Issue: 13
Pages: 1217-1232
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP signaling pathway in remodeling of vessel wall2019
Author(s)
Yoshito Yamashiro, Bui Quoc Thang, Karina Ramirez, Seung Jae Shin, Tomohiro Kohata, Shigeaki Ohata, Tram Anh Vu Nguyen, Sumio Ohtsuki, Kazuaki Nagayama, and Hiromi Yanagisawa
Organizer
GRC on Fibronectin, integrins and related molecules
Related Report
Int'l Joint Research
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