Nonalcoholic steatohepatitis and cardiovascular disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15881
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Kyoto University
• Principal Investigator: Masashi Miyao 京都大学, 医学研究科, 助教 (90711466)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 法医病理学

Outline of Final Research Achievements

Nonalcoholic steatohepatis is a liver manifestation of a metabolic syndrome. Growing evidence suggests that NASH is an independent risk factor for cardiovascular disease mortality and morbidity. However, the association between NASH and cardiovascular diseases remain elusive. We aimed to investigate the association of NASH and cardiovascular disease progression using several mouse models. We found that sinusoidal endothelial dysfunction plays gatekeeper role for NASH progression and is associated with other metabolic disorders including obesity. We also revealed that Kupffer cells lead to sinusoidal endothelial dysfunction and hepatic stellate cell activation, and ultimately leading to cirrhosis. These data provide new insights into mechanisms for obesity-related metabolic syndrome.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

肥満・NASH・メタボリック症候群は全世界で増え続けており、その予防・治療法開発は持続可能な社会の発展にとって重要である。私たちはモデルマウスを用いた実験研究で、血管内皮障害がNASHを発症してしまう原因となること、肝臓に分布する白血球のKupffer細胞が内皮障害を起こす原因となることを明らかにした。このように、NASHの病態に関連するものを明らかにしていくことで、メタボリック症候群によって死亡してしまう人を一人でも多く減らすことに貢献したい。