Mindin, which is a highly conserved extracellular matrix protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes, and immune responses. The aim of the present study was to assess whether mindin contributes to the development of atherosclerosis. A significant up-regulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE−/− mice after high-fat diet treatment. Mindin−/−ApoE−/− mice and macrophage-specific mindin overexpression in ApoE−/− mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis. The Mindin−/−ApoE−/− mice exhibited significantly ameliorated atherosclerotic burdens in the entire aorta and aortic root and increased atherosclerotic plaque stability. Moreover, bone marrow transplantation further demonstrated that mindin deficiency in macrophages was largely responsible for the alleviated atherogenesis. The Lyz2-mindin-TG mice exhibited the opposite phenotype. Mindin deficiency enhanced foam cell formation by increasing the expression of cholesterol effectors, including ABCA1 and ABCG1. The mechanistic study indicated that mindin ablation promoted LXR-β expression via a direct interaction. Importantly, LXR-β inhibition largely reversed the ameliorating effect of mindin deficiency on foam cell formation and ABCA1 and ABCG1 expression. The present study demonstrated that mindin deficiency serves as a novel mediator that protects against foam cell formation and atherosclerosis by directly interacting with LXR-β.
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Double immunofluorescence staining for mindin (red) and CD68 (green) in atherosclerotic plaques of HFD-treated APOE-/- mice. In Issue 11 of Clinical Science, Zhu et al. discuss mindin deficiency as a novel mediator in protecting against foam cell formation and atherosclerosis, through direct interaction with LXR-β; for details, see pages 1199–1213.
Research Article|
June 15 2018
Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-β
Cheng Zhang;
Cheng Zhang
*
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
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Juan-Juan Qin;
Juan-Juan Qin
*
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan 430060, China
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Fu-Han Gong;
Fu-Han Gong
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
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Jing-Jing Tong;
Jing-Jing Tong
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
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Wen-Lin Cheng;
Wen-Lin Cheng
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
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Haiping Wang;
Haiping Wang
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan 430060, China
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Yan Zhang;
Yan Zhang
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan 430060, China
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Xueyong Zhu;
Xueyong Zhu
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan 430060, China
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Zhi-Gang She;
Zhi-Gang She
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Hao Xia;
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
Correspondence: Hao Xia ([email protected]) or Li-Hua Zhu ([email protected])
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Li-Hua Zhu
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China
Correspondence: Hao Xia ([email protected]) or Li-Hua Zhu ([email protected])
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Publisher: Portland Press Ltd
Received:
January 16 2018
Revision Received:
April 21 2018
Accepted:
April 25 2018
Accepted Manuscript online:
April 25 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (11): 1199–1213.
Article history
Received:
January 16 2018
Revision Received:
April 21 2018
Accepted:
April 25 2018
Accepted Manuscript online:
April 25 2018
Connected Content
A commentary has been published:
‘Blow my mind(in)’ – mindin neutralization for the prevention of atherosclerosis?
Citation
Cheng Zhang, Juan-Juan Qin, Fu-Han Gong, Jing-Jing Tong, Wen-Lin Cheng, Haiping Wang, Yan Zhang, Xueyong Zhu, Zhi-Gang She, Hao Xia, Li-Hua Zhu; Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-β. Clin Sci (Lond) 14 June 2018; 132 (11): 1199–1213. doi: https://doi.org/10.1042/CS20180033
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