Toward the creation of a model of chronic obstructive pulmonary disease using mice with atherosclerosis and the establishment of novel therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16114
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: YASUI Hideki 浜松医科大学, 医学部附属病院, 特任講師 (60804937)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 慢性閉塞性肺疾患 / 動脈硬化

Outline of Final Research Achievements

Atherosclerotic disease is an important comorbidity of chronic obstructive pulmonary disease (COPD). We focused on the influence of atherosclerosis on the pathogenesis of COPD and the potential role of plasminogen activator inhibitor-1 (PAI-1) as a link between the two. We established a model of COPD in which mice were treated with cigarette smoke extract, which was characterized by high plasma PAI-1 activity. Next, we established this model of COPD in a mouse model of atherosclerosis (LDLr－/－/Apobec1－/－) that reproduces the characteristics of human dyslipidemia. The arteriosclerotic mice showed more rapid development of emphysema in their lungs than wild-type mice.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

COPDにおいて動脈硬化性疾患は，重要な併存症であり，動脈硬化の存在がCOPDの病態形成に及ぼす影響を解明すること，および両者を結ぶメカニズムを解明することは極めて重要な課題である．我々は，CSE投与により，血漿中のPAI-1活性上昇を伴うCOPDモデルを確立した．ヒトの脂質異常症を再現した動脈硬化マウスでCOPDモデルを作成した際に，野生型と比較しCOPDの肺組織の特徴である肺気腫形成が助長されることを確認し，動脈硬化の存在がCOPDの病態形成を促進する可能性を示した．高齢患者が多いCOPDでは，動脈硬化に着目したCOPDの新規治療戦略の開発は社会的意義が高いものと考えられる．