Mechanisms of thrombus formation and propagation in the onset of atherothrombosis
| Project/Area Number |
16H05163
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | University of Miyazaki |
|---|
Principal Investigator |
Asada Yujiro 宮崎大学, 医学部, 教授 (70202588)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
佐藤 勇一郎 宮崎大学, 医学部, 准教授 (90347055)
山下 篤 宮崎大学, 医学部, 准教授 (90372797)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
|
|---|
| Keywords | アテローム血栓症 / 病理学 |
|---|
| Outline of Final Research Achievements |
In order to clarify the pathogenesis of atherothrombosis, we investigated the mechanisms of thrombus formation/propagation on disrupted plaques from the viewpoint of pathomorphology, metabolic changes and rheology.
Because occlusive thrombi have a predominantly higher proportion of fibrin than non-occlusive ones, large contribution of the coagulation system is considered to be critical in the atherothrombosis. We demonstrated that tissue factor expression in plaques was promoted by many factors including inflammatory cytokines, hypoxia and kynurenine. In addition, about 60% of the cases of acute myocardial infarction were found to have organized thrombi suggesting the progress of several days to weeks from plaque disruption to the onset, and we clarified the contribution of blood flow alteration to thrombus propagation. We tried to visualize plaques with high thrombogenecity and proceeded with plaque evaluation by nuclear medicine and MRI.
|
| Academic Significance and Societal Importance of the Research Achievements |
アテローム血栓症は、我国の死因の約３割を占める重要な疾患で、有効な予防・治療法の確立に向けた発症病態の解明は、医療経済の観点からも急務の課題となっている。本疾患は動脈硬化性プラークの破綻に伴う血栓によって発症するが、血栓形成の機序はまだ不明な点が多い。動脈の血栓は従来より血小板が主体とされてきたが、本研究結果は、発症には凝固系の寄与が重要で、プラークの形状や血流変動が血栓の増大に寄与することを示した。また血栓能の高いプラークの画像診断に有用なマーカーの検索を進め、数種類の候補物質を抽出した。これらの結果は、アテローム血栓症の病態解明と診断のみならず予防・治療への展開に有用である。
|
Report
(4 results)
Research Products
(30 results)
-
-
-
-
-
-
-
-
[Journal Article] A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity2017
Author(s)
Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, Haruna Kouriki, Tetsuko Nakaniwa, Yoshinori Hagiwara, Jiro Harada, Hideaki Sato, Toshimasa Yamazaki, Yoichi Sakakibara, Masahito Suiko, Yujiro Asada, Yasuhiro Takahashi, Ken Yamamoto, Keiichi Fukuyama, Masakazu Sugishima, and Kei Wada
-
Journal Title
Nat. Commun.
Volume: 8
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits.2017
Author(s)
Matsuura Y, Yamashita A, Zhao Y, Iwakiri T, Yamasaki K, Sugita C, Koshimoto C, Kitamura K, Kawai K, Tamaki N, Zhao S, Kuge Y, Asada Y.
-
Journal Title
PLoS One.
Volume: 12
Issue: 4
Pages: e0175976-e0175976
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
[Presentation] Alteration of glycolysis metabolite levels and impaired hypoxic response in diabetic atherosclerosis2017
Author(s)
Yamashita A, Matsuura Y,Zhao Y, Iwakiri T, Yamasaki K,Sugita C, Koshimoto C, Kitamura K, Kawai K, Tamaki N, Zhao S, Kuge Y, AsadaY.
Organizer
ATVB/PVD2017
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
