BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice

Shinichi Tanaka, Takuya Matsumoto, Yutaka Matsubara, Yui Harada, Ryoichi Kyuragi, Jun ichiro Koga, Kensuke Egashira, Yutaka Nakashima, Yoshikazu Yonemitsu, Yoshihiko Maehara

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 (BubR1L/L) and apolipoprotein E-deficient (ApoE-/-) mice (BubR1L/L-ApoE-/- mice) to investigate the effects of BubR1 on atherosclerosis. Methods and Results: Eight-week-old male BubR1L/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 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. 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.

Original languageEnglish
Article numbere004081
JournalJournal of the American Heart Association
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 2016

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this