Elucidation of a new mechanism involved in the pathogenesis of atherosclerosis based on the oxLDL kinetic imaging

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K01309
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Nakano Atsushi 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (90217787)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 動脈硬化 / 骨格筋 / 褐色脂肪 / 酸化LDL / 運動負荷

Outline of Final Research Achievements

The whole-body imaging studies were performed using several strains of oxLDL receptor KO mice. We found that oxLDL accumulation to brown adipocyte tissues, skeletal muscle and other organs except the liver and spleen became completely disappeared in one strain. In contrast, the accumulation to liver and spleen were nearly doubled to compared to the WT mice.
Increased clearance associated with activation of brown adipocyte tissue or skeletal muscle were observed.
In addition, we studied the relationship between exercise load and arteriosclerosis with this receptor. The exercise group had a healthy long life; however, it was observed larger area of atherosclerosis in the aorta. Although this receptor works for oxLDL clearance, it was also expressed in macrophages, in which was considered to made lager area of atherosclerosis.

Free Research Field

血管生理学

Academic Significance and Societal Importance of the Research Achievements

近年着目されている褐色脂肪であるが、従来から言われているエネルギー代謝経路のみならず、体内の廃棄物である酸化LDLのクリアランスにも大きく関わっていることを受容体レベルから明らかにした。さらに、同受容体は骨格筋にも発現しており、運動負荷などの骨格筋の活性化により酸化LDLの取込量は上昇することが判った。また動脈硬化症モデルマウスを使っての実験を行い、運動と動脈硬化の関係も明らかになってきた。
本研究を進めることにより、古くから言われている「適度な運動が身体に良い」についての科学的な裏付けや運動量の最適化等を行うことができ、健康長寿への指標とすることができると考えている。