Novel therapeutic strategy for atherosclerosis by regulating myeloid lineage cells in socially defeated mice

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yamada Hiroyuki 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00240036)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: うつ病 / 動脈硬化 / 好中球細胞外トラップ

Outline of Final Research Achievements

Depression is an independent risk factor of cardiovascular disease (CVD); however, the causal association remains undefined. We exposed mice to repeated social defeat (RSD) to precipitate depressive-like behaviors, and investigated the effects on atherosclerosis. Defeated mice showed higher increase in atherosclerotic lesion areas in the aortic root and entire aorta than control mice. While Ly-6G- and Mac3-positive areas in the aortic root were comparable between the groups, citrullinated histone H3 (Cit-H3)- and myeloperoxidase (MPO)-positive areas, markers of neutrophil extracellular traps (NETs), were significantly increased in the defeated mice. Treatment with DNase I completely diminished the exaggerated atherosclerosis. Our findings demonstrate that exposure to RSD promotes atherosclerosis by augmenting NETs formation within the plaque. This provides new insight into the underlying mechanism of depression-related CVD.

Free Research Field

内科学