The role of PCSK9 in the pathology of acute aortic dissection

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Keio University
• Principal Investigator: Iida Yasunori 慶應義塾大学, 医学部(信濃町), 特任助教 (50408134)
• Co-Investigator(Kenkyū-buntansha): 田中 宏樹 浜松医科大学, 医学部, 特任研究員 (50456563)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大動脈解離 / 炎症 / 脂質異常症 / PSCK9

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.

Free Research Field

大動脈解離

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。