The role of PCSK9 in the pathology of acute aortic dissection
| Project/Area Number |
17K10765
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular surgery
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| Research Institution | Keio University |
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Principal Investigator |
Iida Yasunori 慶應義塾大学, 医学部(信濃町), 特任助教 (50408134)
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| Co-Investigator(Kenkyū-buntansha) |
田中 宏樹 浜松医科大学, 医学部, 特任研究員 (50456563)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 大動脈解離 / 炎症 / 脂質異常症 / PSCK9 / 急性大動脈解離 / PCSK9 / 薬物療法 / 抗凝固療法 / 脂質代謝異常 / 外科 / 薬理学 / 酵素 |
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| Outline of Final Research Achievements |
The pathological and histological examination of the vascular wall tissue of human aortic dissection was performed, and it was confirmed that PCSK9 was overexpressed especially in the media. Furthermore, we discovered and reported that PCSK9 secretion was derived from synthetic smooth muscle cells among medial smooth muscle cells. This is the first knowledge in Japan and abroad.
The mouse aortic dissection model was initially general, but the underlying dyslipidemic mouse had ApoE knockout, and this is the type III dyslipidemia in humans, which was fairly rare disease type. Therefore, we created a mouse with Type IIa (the most common dyslipidemia in humans) and performed the same experimental manipulation as last year to induce aortic dissection. This knowledge was also the first in Japan and abroad.
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| Academic Significance and Societal Importance of the Research Achievements |
今まで大動脈解離は動脈硬化が原因と言われ続けてきたが、虚血性心疾患や、閉塞性動脈硬化症など、血管が「狭く」なる(狭窄)を引き起こす原因も動脈硬化と言われており、血管が「裂ける」疾患と病因が同じであることはおかしいと考えてきた。この研究を通して、大動脈解離と「炎症」との関係が明らかとなり、炎症が動脈壁の特に中膜に及んでいることが分かった。動脈硬化は主に内膜に病変を認めることから考えると、この研究成果は今後動脈解離の研究において有意義なものとなると考えられた。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Inhibition of VEGF (Vascular Endothelial Growth Factor)-A or its Receptor Activity Suppresses Experimental Aneurysm Progression in the Aortic Elastase Infusion Model2019
Author(s)
Xu B, Iida Y, Glover KJ, Ge Y, Wang Y, Xuan H, Hu X, Tanaka H, Wang W, Fujimura N, Miyata M, Shoji T, Guo J, Zheng X, Gerritsen M, Kuo C, Michie SA, Dalman RL
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 39
Issue: 8
Pages: 1652-1666
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II-Induced Mice.2018
Author(s)
Tanaka H, Iida Y, Iwaki T, Suzuki Y, Sano H, Miyajima C, Zaima N, Sasaki T, Sumioka A, Hakamata S, Shimizu H, Umemura K, Urano T.
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Journal Title
Ann Vasc Surg.
Volume: 48
Pages: 204-213
DOI
Related Report
Peer Reviewed
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