Development of novel therapy for cardiac amyloidosis by identifying transthyretin-derived amyloid fibril deposition promoting factor
Project/Area Number |
19K08493
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Osaka City University |
Principal Investigator |
Izumiya Yasuhiro 大阪市立大学, 大学院医学研究科, 准教授 (10515414)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 心アミロイドーシス / 遺伝子発現 / 心筋生検 / 心臓MRI / トランスサイレチン型心アミロイドーシス / 沈着促進因子 / 網羅的解析 |
Outline of Research at the Start |
心不全の原因疾患として,これまで希少疾患と考えられてきた心アミロイドーシス,その中でも野生型トランスサイレチンアミロイドーシス(wild-type transthyretin amyloidosis: ATTRwt)の占める割合が予想以上に多いことが明らかになってきた. ATTRwtに対する治療法の開発はこれまでトランスサイレチン(TTR)を標的としたものばかりであり,アミロイド線維が沈着する心臓の微小環境に着目した研究は皆無である.本研究により,TTR由来のアミロイドの沈着促進因子を明らかにすることができれば,その因子をターゲットとした新規治療法の開発に繋がると考えられる.
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Outline of Final Research Achievements |
The mechanism of the onset and progression of transthyretin cardiac amyloidosis (ATTR-CA) is still unknown. In this study, we compared gene expression profile in endomyocardial biopsy samples obtained from patients with ATTR-CA and hypertrophic cardiomyopathy (HCM) by next-generation sequencing. There were 392 genes, included adhesion molecules, were upregulated in endomyocardial biopsy samples derived from ATTR-CA compared with HCM. On the other hand, there were 309 genes, including inflammatory cytokine receptor heat shock proteins, were downregulated in cardiac sample derived from ATTR-CA compared with HCM. These alteration in gene expression might involved in the onset and progression of ATTR-CA.
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Academic Significance and Societal Importance of the Research Achievements |
心不全の基礎疾患として野生型トランスサイレチンアミロイドーシス(wild-type transthyretin amyloidosis: ATTRwt)が予想以上に多いことが明らかになってきた。これまでのATTRwtに対する治療法は、沈着物質となるトランスサイレチンを標的とするものが多く、沈着臓器である心臓側から見た治療法の開発は皆無であった。本研究成果により、トランスサイレチン由来のアミロイド線維が沈着しやすい心臓の遺伝子発現が明らかとなった。これらの遺伝子の機能解析を進めることで、新しい側面から見たATTRwtの治療法の開発に繋がると考えられる。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Japanese Circulation Society Joint Working Group. JCS 2020 Guideline on Diagnosis and Treatment of Cardiac Amyloidosis.2020
Author(s)
Kitaoka H, Izumi C, Izumiya Y, Inomata T, Ueda M, Kubo T, Koyama J, Sano M, Sekijima Y, Tahara N, Tsukada N, Tsujita K, Tsutsui H, Tomita T, Amano M, Endo J, Okada A, Oda S, Takashio S, Baba Y, Misumi Y, Yazaki M, Anzai T, Ando Y, Isobe M, Kimura T, Fukuda K
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Journal Title
Circ J.
Volume: 84
Pages: 1610-1671
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure.2020
Author(s)
Ishikawa H, Izumiya Y, Shibata A, Ichikawa Y, Yamaguchi T, Yamaguchi Y, Kitada R, Iwata S, Ehara S, Tomita S, Hanatani A, Yoshiyama M.
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Journal Title
Heart Vessels.
Volume: 35
Issue: 5
Pages: 681-688
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Successful catheter ablation improves exercise tolerance in persistent atrial fibrillation patients, especially those with reduced ventricular contraction, preserved atrial function, or a high CHADS2 score.2020
Author(s)
Katayama H, Shibata A, Doi A, Ishikawa H, Tamura S, Yamaguchi Y, Matsuo M, Yoshiyama T, Tatsumi H, Iwata S, Ehara S, Izumiya Y, Yoshiyama M.
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Journal Title
J Cardiol.
Volume: 75
Issue: 5
Pages: 529-536
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Combination of Commonly Examined Parameters Is a Useful Predictor of Positive <sup>99 m</sup>Tc-Labeled Pyrophosphate Scintigraphy Findings in Elderly Patients With Suspected Transthyretin Cardiac Amyloidosis2019
Author(s)
Marume K, Takashio S, Nishi M, Hirakawa K, Yamamoto M, Hanatani S, Oda S, Utsunomiya D, Shiraishi S, Ueda M, Yamashita T, Sakamoto K, Yamamoto E, Kaikita K, Izumiya Y, Yamashita Y, Ando Y, Tsujita K.
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Journal Title
Circulation Journal
Volume: 83
Issue: 8
Pages: 1698-1708
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2019-07-25
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical potential of dual-energy cardiac CT in cardiac amyloidosis.2019
Author(s)
Oda S, Nakaura T, Utsunomiya D, Hirakawa K, Takashio S, Izumiya Y, Tsujita K, Kawano Y, Okuno Y, Hata H, Matsuoka M, Yamashita T, Ueda M, Ando Y, Yamashita Y.
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Journal Title
Amyloid.
Volume: 26
Issue: sup1
Pages: 91-92
DOI
Related Report
Peer Reviewed / Open Access
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