BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E‐Deficient Mice. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Tanaka, Shinichi; Matsumoto, Takuya; Matsubara, Yutaka; Harada, Yui; Kyuragi, Ryoichi; Koga, Jun‐ichiro; Egashira, Kensuke; Nakashima, Yutaka; Yonemitsu, Yoshikazu; Maehara, Yoshihiko
• Is Part Of: Journal of the American Heart Association. Volume 5:Issue 9(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-09
• Subjects: atherosclerosis -- cell cycle -- macrophage -- proliferation; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.116.004081
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : 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.