Mechanisms of sarcopenia-induced cardiac function alteration and functional improvement via skeletal muscle regeneration in the ischemic heart.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K10737
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Kyoto Prefectural University of Medicine (2021); Asahikawa Medical College (2018-2020)
• Principal Investigator: Takehara Naofumi 京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (90374793)
• Co-Investigator(Kenkyū-buntansha): 川辺 淳一 旭川医科大学, 医学部, 教授 (10400087) ; 田中 宏樹 旭川医科大学, 医学部, 助教 (70596155)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: サルコペニア / 心臓悪液質 / オートファジー / miRNA / 不全心筋回復障害

Outline of Final Research Achievements

Sarcopenia is a pathophysiological malfunction induced by skeletal muscle atrophy. However, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood. Here, we developed a novel sarcopenia-induced cardiac repair disturbance mouse model induced by tail suspension (TS) after cardiac ischemia and reperfusion (I/R). Then, we identified a specific exosomal-microRNA, miR-16-5p, in the circulating exosomes of I/R-TS mice. Likewise, miR-16-5p disturbed cardiac repair in I/R mice directly. Additionally, in cardiomyocytes (CMs) cultured under hypoxic conditions in the presence of a miR-16-5p, we clarified that autophagosomes were decreased in CMs via SESN1/mTOR inactivation. In conclusion, we show the pro-apoptotic effect of sarcopenia-derived miR-16-5p, which may be behind the exacerbation of myocardial infarction. Therefore, miR-16-5p can be a novel therapeutic target for cardiac repair disturbances in sarcopenia-cachexia.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

重症心筋梗塞では、長期臥床による、廃用性および心臓悪液質に伴う二次性のサルコペニアを併発することがしばしばあり、骨格筋萎縮に伴うサルコペニアが循環血液中exosome内のmiR-16-5pを介して心機能の回復不全を引き起こす可能性を念頭におくことは疾病管理、治療介入の観点から重要である。そしてサルコペニアを合併した虚血性心疾患患者に対して、運動療法可能な患者においては定量的リハビリテーションを、運動療法困難な患者、特に高齢者に対しては骨格筋萎縮への予防的治療として細胞療法を、と異なる選択肢の中から最善の治療戦略を立てることで、患者予後を改善し、医療費削減の一助になることが期待される。