Comprehensive assessment of risk of surgery with novel myokine in patients with aortic valve stenosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19412
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: Hanatani Shinsuke 熊本大学, 大学病院, 非常勤診療医師 (40755443)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マイオカイン / フレイル / サルコペニア / heme oxygenase 1

Outline of Final Research Achievements

We performed proteomic analysis using skeletal muscle samples from Akt1 TG and wild type mice, and identified that heme oxygenase-1(HO-1) was upregulated protein in Akt1 TG mice. Akt1-mediated muscle growth enhanced blood flow recovery after hindlimb ischemia. Treatment with HO-1 inhibitor SnMP abolished the angiogenic effect of skeletal muscle Akt1 activation. On the other hand, blood flow recovery after hindlimb ischemia was similar between wild type and skeletal muscle-specific HO-1-knockout mice. Furthermore, immunohistochemistry showed that HO-1 expression was not increased in muscle cells, but it was increased in macrophages and endothelial cells. These data suggest that Akt1-mediated muscle growth improves blood flow recovery after hindlimb ischemia by enhancing HO-1 expression in neighboring cells.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

骨格筋重量が増加することで発現が増加しかつ遠隔臓器に保護的に作用する因子として、今回heme oxygenase-1(HO-1)の血管新生に対する作用について明らかにした。申請者の以前の報告でも骨格筋重量が増加することで起こる遠隔臓器への保護作用は血管新生を介したものが多く、今回着目したHO-1もその一部を担っているものと推測される。このような因子が明らかになることで、本研究の当初の動機であるフレイルの診断マーカーとしての応用や新規の治療ターゲットとしての有用性も考慮される。