Investigation on the mechanisms of ruptured acute aortic dissection based on immune response analyses
| Project/Area Number |
17K10768
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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 | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木村 直行 自治医科大学, 医学部, 教授 (20382898)
田岡 誠 日本大学, 医学部, 助教 (20814213)
大幸 俊司 日本大学, 医学部, 助教 (20748149)
板垣 翔 自治医科大学, 医学部, 講師 (40639035)
宇野澤 聡 日本大学, 医学部, 助教 (60451324)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 急性大動脈解離 / 大動脈破裂 / 好中球 / 大動脈瘤破裂 / 好中球関連因子 / 白血球 / 炎症反応 / 免疫応答 |
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| Outline of Final Research Achievements |
In 466 patients with acute type A aortic dissection (ATAAD) treated surgically within 48 hours of symptom onset, patients’ white blood cell (WBC) count differed significantly in relation to the extent of dissection. With 11,000/μL used as the cut-off value for WBC count elevation, multivariable analysis showed current smoking (p<0.001, OR:2.79), dissection extending to the iliac artery (p=0.006, OR:1.79), and age (p=0.007, OR:0.98) to be factors related to the elevated WBC count.
Total RNA was isolated from the intima-media layer of dissected ascending aorta obtained intraoperatively from ATAAD patients with unruptured aneurysm (n=5) and with ruptured aneurysm (n=3). Gene expression profiling was performed with mRNA microarrays. Microarray analysis revealed that 816 genes (2.0% of 42,545 probes) were differentially expressed in the rupture group. The top 14 related pathways included inflammatory response, leukocyte migration, leukocyte chemotaxis, and innate immune response.
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| Academic Significance and Societal Importance of the Research Achievements |
急性大動脈解離は、成人突然死の代表的疾患であり、急性期に出現する大動脈破裂が予後に大きな影響を及ぼす。ヒト症例を対象とした急性の炎症反応や大動脈破裂に関する研究は少なく、炎症反応の指標である末梢血白血球数増多に関しても背景因子の報告がなかった。
今回実施した研究により、解剖学的には大動脈解離の遠位側への進展が末梢血白血球増多と関連することが明らかになった。また、急性A型大動脈解離症例の大動脈組織を使用した網羅的遺伝子発現解析研究では、急性期炎症反応経路の発現増強が確認された。今後本研究を更に推進し、大動脈破裂の早期診断や早期治療実施につながるバイオマーカー開発を目指す。
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] Gene expression profiling of acute type A aortic dissection combined with in vitro assessment.2017
Author(s)
Kimura N, Futamura K, Arakawa M, Okada N, Emrich F, Okamura H, Sato T, Shudo Y, Koyano TK, Yamaguchi A, Adachi H, Matsuda A, Kawahito K, Matsumoto K, Fischbein MP.
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Journal Title
European Journal of Cardio-Thoracic Surgery
Volume: 52
Issue: 4
Pages: 810-817
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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