The roles of inflammatory signals in cardiovascular remodeling

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09493
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Takeda Norihiko 東京大学, 医学部附属病院, 特任講師 (40422307)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 心血管リモデリング / 線維化 / 炎症

Outline of Final Research Achievements

In this study, we evaluated the roles of inflammatory processes in cardiovascular remodeling. Using murine model of pressure-overload induced cardiac hypertrophy and fibrosis, we examined the roles of inflammatory macrophages during cardiac remodeling. We also established a murine model of pulmonary artery overflow vasculopathy, where we induced a volume shift of the pulmonary artery leading to the vascular remodeling. Based on the current model, we found that monocyte/ macrophages accumulate to the lung of overflow vasculopathy. We further examined the ischemic environment in fibroblasts activation. Through the genetic or pharmacological approaches, we found that hypoxia inducible factor mediated glycolytic reprograming elicits fibroblast activation. We also identified that serum starved environment accelerate collagen production in in vitro cultured fibroblasts. These results illuminate previously unidentified pathological processes which underlie cardiovascular remodeling.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

高血圧症など生活習慣病では心臓、血管に障害が引きおこされ、心不全などの原因になります。これまで血圧変動などがどのように心血管病を発症させるのか、その病態は十分には分かっていませんでした。本研究では炎症プロセスに着目し、それらが心臓、血管病の発症にどのように関与するかを解析しました。今回の知見をもとに、心血管病に対する新たな治療法を開発する礎となる可能性が期待できると考えています。