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

3 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 1 2016

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Apolipoproteins E
Atherosclerosis
Macrophages
Bone Marrow Cells
Bone Marrow
Cell Cycle Proteins
benzimidazole
Bone Marrow Transplantation
Cell Division
Blood Vessels
Cholesterol
Diet
Phenotype
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice. / Tanaka, Shinichi; Matsumoto, Takuya; Matsubara, Yutaka; Harada, Yui; Kyuragi, Ryoichi; Koga, Jun ichiro; Egashira, Kensuke; Nakashima, Yutaka; Yonemitsu, Yoshikazu; Maehara, Yoshihiko.

In: Journal of the American Heart Association, Vol. 5, No. 9, e004081, 01.09.2016.

Research output: Contribution to journalArticle

Tanaka, Shinichi ; Matsumoto, Takuya ; Matsubara, Yutaka ; Harada, Yui ; Kyuragi, Ryoichi ; Koga, Jun ichiro ; Egashira, Kensuke ; Nakashima, Yutaka ; Yonemitsu, Yoshikazu ; Maehara, Yoshihiko. / BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice. In: Journal of the American Heart Association. 2016 ; Vol. 5, No. 9.
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author = "Shinichi Tanaka and Takuya Matsumoto and Yutaka Matsubara and Yui Harada and Ryoichi Kyuragi and Koga, {Jun ichiro} and Kensuke Egashira and Yutaka Nakashima and Yoshikazu Yonemitsu and Yoshihiko Maehara",
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AU - Harada, Yui

AU - Kyuragi, Ryoichi

AU - Koga, Jun ichiro

AU - Egashira, Kensuke

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N2 - 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.

AB - 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.

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