Role of HMGB1 protein in the pathogenesis of abdominal aortic aneurysm

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: ANZAI Toshihisa 独立行政法人国立循環器病研究センター, 病院, 部長 (60232089)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 循環器・高血圧 / 蛋白質 / 病理学 / 免疫学

Outline of Final Research Achievements

High-mobility group box 1 protein (HMGB1) is a non-histone DNA binding protein and a potent inducer of inflammatory response. We investigated the role of HMGB1 in a mouse CaCl2-induced abdominal aortic aneurysm (AAA) model. Administration of neutralizing anti-HMGB1 antibody for 6 weeks resulted in suppression of AAA formation, inflammatory cellular infiltration, and elastin fragmentation, in association with decreased expression of HMGB1, infiltration of Mac-3 positive macrophages, activity of MMP-2 and MMP-9, and mRNA expression of tumor necrosis factor-α, CD68 and MCP-1 in the aorta. These findings suggest a significant role of HMGB1 in the pathogenesis of AAA through enhanced inflammatory response.

Free Research Field

循環器内科学