The analysis of LYPD1 expression regulatory system for understanding the mechanisms of heart diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02813
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Katsuhisa Matsuura 東京女子医科大学, 医学部, 准教授 (70433993)
• Co-Investigator(Kenkyū-buntansha): 増田 信奈子 東京女子医科大学, 医学部, 助教 (30342851)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管新生抑制因子 / LYPD1 / 線維芽細胞

Outline of Final Research Achievements

Recently, we have identified that heart-derived fibroblasts, unlike other tissue-derived fibroblasts, have a function of suppressing angiogenesis, and that a novel angiogenesis-suppressing factor, LYPD1, is responsible for this. In this study, we investigated why LYPD1 expression is high in heart-derived fibroblasts and the significance of LYPD1 expression in heart disease. As a result of making full use of bioinformatics analysis using comprehensive gene expression data, we succeeded in identifying a transcription factor that suppresses angiogenesis through regulation of LYPD1 expression. We also found that LYPD1, which is highly expressed in the heart, transiently decreases after myocardial infarction, and it was confirmed that administration of LYPD1 neutralizing antibody to myocardial infarction model animals tends to suppress the decrease in left ventricular ejection fraction.

Free Research Field

循環器内科学　再生医学

Academic Significance and Societal Importance of the Research Achievements

線維芽細胞は、様々な組織・臓器に存在し、周囲の細胞の機能調節を通して組織・臓器機能に影響することが知られている。血管新生とは、組織の構造変化や細胞外マトリクスタンパクの分解を伴う現象である。心臓は、拍動によって効率的に血液を拍出し、かつ高い内圧に耐える組織的頑強さも要求される臓器であるため、転写因子レベルで血管新生を高度に負に制御する機構が存在することは、心臓の恒常性を理解する上で大変重要な知見と考えられ、心臓の様々な生理現象と当該転写因子およびLYPD1発現との関連の検証が今後必要と考える。また一過性のLYPD1抑制は、虚血性心疾患に対する新たな血管新生治療に繋がるものと考える。