The effect of progranulin on aging-related cardiac hypertrophy and heart failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Osaka University
• Principal Investigator: Ohama Tohru 大阪大学, 歯学研究科, 助教 (20467583)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: progranulin / cadiac hypertrophy / heart failure / beta catenin / aging

Outline of Final Research Achievements

Progranulin(PGRN) have been reported that its mutation might be associated with accelerated brain aging, leading to some types of dementia in the neuroscience field. We examine whether PGRN is related to aging-associated cardiac hypertrophy/heart failure and atherosclerosis. PGRN deficiency leads to accelerated aging in the cardiomyocyte and exhibits more severe cardiac hypertrophy and heart failure compared with control mice, possibly due to beta catenin activation.　We also show that PGRN deletion enhances development of atherosclerosis, possibly due to lysosomal/autophagy dysfunction.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

本邦における高齢化社会がこの先も進んでいくと思われる。その中で認知症患者も同時に増加が見込まれるが、Progranulin(PGRN)変異と認知症患者との関連が示唆され、変異により老化が促進することが報告されていた。我々は老化に伴い、心肥大、心不全が今後も間違いなく増加すると思われるが、PGRN欠損による心不全、動脈硬化発症のメカニズムを見出し、老化に伴うこれらの疾患の治療ターゲットの一つを見出したことは学術的にも社会的にも意義は大きいものと考えられる。