A diagnostic approach for lethal cardiac hypertrophy based on the analysis of autophagy-lysosomal pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17419
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Tokai University
• Principal Investigator: KAKIMOTO Yu 東海大学, 医学部, 講師 (40734166)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 心臓性突然死 / 心肥大 / オートファジー / リソソーム / リポフスチン / カテプシン / 年齢推定

Outline of Final Research Achievements

It was revealed that myocardial lipofuscin (LF) is useful for age estimation. The amount of LF is increased in cancer but unchanged in sudden cardiac death. LF accumulation is not correlated with the amount of LC3-II or p62, which indicates that LF is not a direct biomarker for autophagy dysfunction.
The major proteasomes of lysosomes, CTSB and CTSD increased in aging, but the levels of p62、ATP synthase, andα-synuclein were unchanged. In sudden cardiac death with cardiac hypertrophy, CTSD was significantly decreased, but the levels of p62、ATP synthase, andα-synuclein were unchanged.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

心筋のLF定量は、通常の組織標本作成と並行して行える検査であるため、身元不明者の年齢推定に役立てられる。また、本研究では癌などの慢性疾患でのLF増加が示唆されたことから死因究明にも活用できると考えらえる。
リソソームのタンパク質分解酵素については、CTSDの減少が心臓性突然死のリスクマーカーとなる可能性が示され、生理的心肥大と病的心肥大の鑑別への活用が期待される。