Investigation of mechanisms and regulatory pathways of p27kip expression in macrophages and the role of p27kip in the pathogenesis of atherosclerosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19519
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: Ishii Norio 熊本大学, 医学部附属病院, 特任助教 (10599111)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 動脈硬化 / 脂質代謝異常 / マクロファージ

Outline of Final Research Achievements

As for the pathophysiological significance of the macrophage proliferation in the atherosclerosis, there are still many questions left to be answered. To verify the direct evidence of involvement of local macrophage proliferation for atherosclerosis, we generated transgenic mice received p27kip expression only in the macrophages(mac-p27Tg), whose macrophage proliferation was specifically inhibited. The aortic valve annulus section average plaque area was significantly reduced in mac-p27Tg, compared with that of the control. The percentage of the necrotic core to the total advanced lesion area significantly decreased in mac-p27Tg. The inflammatory cytokines were also reduced in mac-p27Tg. We found that the local macrophage proliferation could be one of the common underlying pathophysiological features in the formation and the progression of atherosclerosis. Our results might lead to the control of the macrophage proliferation as the therapeutic target for atherosclerotic disease.

Free Research Field

医歯薬学