Elucidation of cross-talk mechanism between heart and skeletal-muscle in ischemic heart disease with sarcopenia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19824
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Hayasaka Taiki 旭川医科大学, 医学部, 特任助教 (10838543)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: サルコペニア / マイクロRNA / 心疾患 / 心筋骨格筋連関

Outline of Final Research Achievements

We developed a novel sarcopenia‐induced cardiac repair disturbance mouse model induced by tail suspension (TS) after cardiac ischemia and reperfusion (I/R). Importantly, we identified a specific exosomal‐microRNA marker, miR‐16‐5p, in the circulating exosomes of I/R‐TS mice. Of note, sarcopenia after I/R disturbed cardiac repair and raised the level of circulating‐exosomal‐miR‐16‐5p secreting from both the atrophic limbs and heart of TS mice. Likewise, miR‐16‐5p mimic plasmid disturbed cardiac repair in I/R mice directly. Additionally, in neonatal rat ventricular myocytes (NRVMs) cultured in vitro under hypoxic conditions in the presence of a miR‐16‐5p mimic, we observed increased apoptosis, and also clarified that autophagosomes were decreased via SESN1 transcript interference‐mediated mTOR activation. In conclusion, we show the pro‐apoptotic effect of sarcopenia‐derived miR‐16‐5p, which may be behind the exacerbation of myocardial infarction.

Free Research Field

心臓微小環境

Academic Significance and Societal Importance of the Research Achievements

骨格筋萎縮を有する心疾患患者の予後は悪いことが知られており、虚血性心疾患後の不活動に伴う筋萎縮に対してはリハビリテーションの重要性が臨床的に明らかとなっていた。しかしながら、骨格筋萎縮が心疾患に与える悪影響についての詳細なメカニズムの詳細は不明だった。今回我々はmiR-16-5pの分泌を介したSESN1-mTOR経路がサルコペニアを合併した虚血性心疾患のアポトーシス亢進を起こすという、心臓微小環境の新たなメカニズムを明らかとした。miR-16-5pはサルコペニア合併心疾患の予後予測マーカーのみならず、これを介した虚血性心疾患の増悪経路に対する新たな治療ターゲットの可能性を有している。