Open AccessBubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E‐Deficient Mice
Author(s) -
Tanaka Shinichi,
Matsumoto Takuya,
Matsubara Yutaka,
Harada Yui,
Kyuragi Ryoichi,
Koga Junichiro,
Egashira Kensuke,
Nakashima Yutaka,
Yonemitsu Yoshikazu,
Maehara Yoshihiko
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.004081
Subject(s) - medicine , macrophage , apolipoprotein e , apolipoprotein b , endocrinology , immunology , cholesterol , disease , in vitro , genetics , biology
Background Budding uninhibited by benzimidazole‐related 1 (BubR1), a cell cycle–related protein, is an essential component of the spindle checkpoint that regulates cell division. BubR1 insufficiency causes early aging‐associated vascular phenotypes. We generated low‐ BubR1 ‐expressing mutant ( BubR1 L/L ) and apolipoprotein E‐deficient ( ApoE −/− ) mice ( BubR1 L/L ‐ApoE −/− mice) to investigate the effects of BubR1 on atherosclerosis. Methods and Results Eight‐week‐old male BubR1 L/L ‐ApoE −/− mice and age‐matched ApoE −/− mice were used in this study. Atherosclerotic lesion development after being fed a high‐cholesterol diet for 12 weeks was inhibited in BubR1 L/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 BubR1 L/L ‐ApoE −/− mice. Decreased BubR1 in bone marrow cells and non‐bone marrow–derived cells decreased the atherosclerotic burden. In vitro assays indicated that decreased BubR1 expression impaired proliferation, but not migration, of bone marrow–derived macrophages. Conclusions BubR1 may represent a promising new target for regulating atherosclerosis.