CKIP-1 limits foam cell formation and inhibits atherosclerosis by promoting degradation of Oct-1 by REGγ

Jiao Fan, Lifeng Liu, Qingyan Liu, Yu Cui, Binwei Yao, Minghua Zhang, Yabing Gao, Yesheng Fu, Hongmiao Dai, Jingkun Pan, Ya Qiu, Cui Hua Liu, Fuchu He, Yu Wang () and Lingqiang Zhang ()
Additional contact information
Jiao Fan: Beijing Institute of Lifeomics
Lifeng Liu: Chinese PLA General Hospital
Qingyan Liu: 302 Military Hospital of China
Yu Cui: Beijing Institute of Lifeomics
Binwei Yao: Beijing Institute of Radiation Medicine
Minghua Zhang: Chinese PLA General Hospital
Yabing Gao: Beijing Institute of Radiation Medicine
Yesheng Fu: Beijing Institute of Lifeomics
Hongmiao Dai: Beijing Institute of Lifeomics
Jingkun Pan: Chinese PLA General Hospital
Ya Qiu: Chinese PLA General Hospital
Cui Hua Liu: Chinese Academy of Sciences
Fuchu He: Beijing Institute of Lifeomics
Yu Wang: Chinese PLA General Hospital
Lingqiang Zhang: Beijing Institute of Lifeomics

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Atherosclerosis-related cardiovascular diseases are the leading cause of mortality worldwide. Macrophages uptake modified lipoproteins and transform into foam cells, triggering an inflammatory response and thereby promoting plaque formation. Here we show that casein kinase 2-interacting protein-1 (CKIP-1) is a suppressor of foam cell formation and atherosclerosis. Ckip-1 deficiency in mice leads to increased lipoprotein uptake and foam cell formation, indicating a protective role of CKIP-1 in this process. Ablation of Ckip-1 specifically upregulates the transcription of scavenger receptor LOX-1, but not that of CD36 and SR-A. Mechanistically, CKIP-1 interacts with the proteasome activator REGγ and targets the transcriptional factor Oct-1 for degradation, thereby suppressing the transcription of LOX-1 by Oct-1. Moreover, Ckip-1-deficient mice undergo accelerated atherosclerosis, and bone marrow transplantation reveals that Ckip-1 deficiency in hematopoietic cells is sufficient to increase atherosclerotic plaque formation. Therefore, CKIP-1 plays an essential anti-atherosclerotic role through regulation of foam cell formation and cholesterol metabolism.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07895-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07895-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07895-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().