Role of IL-22/IL-22BP in the pathogenesis of left ventricular diastolic dysfunction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17101
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kurume University
• Principal Investigator: Yamamoto Mai 久留米大学, 医学部, 助教 (90830026)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IL-22 / 左室拡張障害 / 心肥大 / STAT3

Outline of Final Research Achievements

The purpose of this study is to clarify the role of interleukin 22 (IL-22) and its potent endogenous inhibitor, IL-22 binding protein (IL-22BP), in the pathogenesis of left ventricular diastolic dysfunction. In WT mice, 2 weeks AngII infusion increased E/e', whereas no increase in E/e' was observed in IL-22KO mice. Furthermore, in IL-22KO mice, increased heart weight/body weight ratio, ventricular wall thickening, and left ventricular diastolic dysfunction induced by AngII were suppressed. Thus, IL-22 may be the factor for cardiac hypertrophy and left ventricular diastolic dysfunction.On the other hand, IL-22BP deletion did not affect Ang II-induced left ventricular diastolic dysfunction.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

超高齢社会に突入した我が国では、高齢者心不全の爆発的な増加に直面している。中でも左室駆出率が保たれた心不全（HFpEF; Heart failure with preserved ejection fraction）は高齢者に多く、その割合が急増しているが、HFpEFの予後改善につながる確固たる治療法は確立されていない。本研究により、IL-22が心室リモデリングやHFpEFの重要な病態である左室拡張障害を起こすことが示された。IL-22による左室拡張障害増悪メカニズムが解明されることで、HFpEFの予防や予後改善につながる新たな治療戦略発展に役立つと期待できる。