Role of age-associated BubR1 gene in atherogenesis and its molecular mechanism

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Kyushu University
• Principal Investigator: Matsumoto Takuya 九州大学, 大学病院, 講師 (20374168)
• Co-Investigator(Kenkyū-buntansha): MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662) ; FURUYAMA Tadashi 九州大学, 大学病院, 助教 (00419590) ; FUKUNAGA Ryota 九州大学, 大学病院, 助教 (00529860)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 細胞周期 / 動脈硬化 / マクロファージ / 増殖

Outline of Final Research Achievements

BubR1 is an essential component of the spindle checkpoint. BubR1 insufficiency causes early aging-associated vascular phenotypes. We generated low-BubR1-expressing mutant (BubR1L/L) and apolipoprotein E-deficient (ApoE-/-) mice (BubR1L/L-ApoE-/- mice) to investigate the effects of BubR1 on atherosclerosis. 8W old male BubR1L/L-ApoE-/- mice and age-matched ApoE-/- mice were used. Atherosclerotic lesion development after being fed a high-cholesterol diet for 12 weeks was inhibited in BubR1L/L-ApoE-/- mice compared with ApoE-/- mice, and was accompanied by decreased accumulation of macrophages. To address the relative contribution of BubR1 on bone marrow-derived cells compared with non-bone marrow-derived cells, we performed bone marrow transplantation in ApoE-/- and BubR1L/L-ApoE-/- mice. Decreased BubR1 in bone marrow cells and non-bone marrow-derived cells decreased the atherosclerotic burden. BubR1 may represent a promising new target for regulating atherosclerosis.

Free Research Field

血管外科