Functional analysis of macrophage CYLD in age-related atherogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08914
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Osaka University
• Principal Investigator: Takami Yoichi 大阪大学, 医学系研究科, 助教 (90621756)
• Co-Investigator(Kenkyū-buntansha): 樂木 宏実 大阪大学, 医学系研究科, 教授 (20252679) ; 中神 啓徳 大阪大学, 医学系研究科, 寄附講座教授 (20325369)
• Research Collaborator: YAMAMOTO Koichi 大阪大学, 医学系研究科, 講師 (00528424)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: CYLD / 脱ユビキチン化酵素 / 動脈硬化 / 老化 / マクロファージ / 血管内皮 / 炎症

Outline of Final Research Achievements

Endothelial cells (EC) and macrophages (Mf) play pivotal roles in the early stage of atherogenesis. Inflammatory stimuli induced CYLD expression in these cells. Knockdown of CYLD in EC induced the expression of inflammatory and adhesion molecules, followed by increased monocytes adhesion. Knockdown of CYLD in Mf induced the expression of inflammatory as well as foam cell formation along with increased expression of scavenger receptors, lipid chaperones and lipid synthase and decreased expression of lipid efflux-related molecule. Intriguingly, CYLD expression was significantly reduced in EC which met replicative senescence and bone marrow-derived Mf harvested from aged mice. CYLD in the vasculature could be a novel therapeutic target molecule, especially in the early preventive intervention against the initiation of age-related atherogenesis.

Free Research Field

血管生物学