Development of novel therapy for cardiac amyloidosis by identifying transthyretin-derived amyloid fibril deposition promoting factor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08493
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 心アミロイドーシス / 遺伝子発現 / 心筋生検

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.

Free Research Field

循環器内科

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。