Regulation of Heart Failure Pathophysiology by Immune Checkpoint Mechanisms

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Osaka University
• Principal Investigator: Kawamura Ai 大阪大学, 医学部附属病院, 助教 (10838923)
• Co-Investigator(Kenkyū-buntansha): 河村 拓史 大阪大学, 医学系研究科, 助教 (60839398) ; 秦 広樹 大阪大学, 医学系研究科, 特任准教授(常勤) (80638198)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 重症心不全 / 左室補助人工心臓 / 左室unloading / 免疫チェックポイント機構

Outline of Final Research Achievements

In myocardial tissue samples extracted from patients with left ventricle unloading by a left ventricular assist device, increased expression of PD-L1 was observed. The expression level of PD-L1 was positively correlated with the expression level of aPKCλ / c-Myc and left ventricular ejection fraction, and negatively correlated with left ventricular end-diastolic diameter and left ventricular end-systolic diameter. Increased expression of PD-L1 / aPKCλ / c-Myc was also observed in human umbilical cord blood-derived vascular endothelial cells after unloading with an in vitro model, in which grounded cultured cells are expanded and unloaded in a stretch chamber.
These results suggest that aPKCλ / c-Myc / PD-L1 expression are upregulated in vascular endothelial cells by left ventricular unloading, which may contribute to left ventricular remodeling.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

慢性心不全の病態における免疫チェックポイント機構の果たす役割についてはほとんど研究がなされていない。PD-L1による心不全の病態制御機構が明らかとなれば、新たな視点から重症心不全の治療戦略を開発することも可能であり、学術的・社会的意義は大きいと考えられる。