Format

Send to

Choose Destination
FASEB J. 2017 Mar;31(3):1097-1106. doi: 10.1096/fj.201601030R. Epub 2016 Dec 7.

Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis.

Huo M1,2,3, Huang Y1,2,3, Qu D1,2,3, Zhang H1,2,3, Wong WT4, Chawla A5,6,7, Huang Y1,2,3, Tian XY8,2,3.

Author information

1
Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.
2
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
3
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
4
School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China.
5
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
6
Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
7
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
8
Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong; xytian@cuhk.edu.hk.

Abstract

BMAL1, the nonredundant transcription factor in the core molecular clock, has been implicated in cardiometabolic diseases in mice and humans. BMAL1 controls the cyclic trafficking of Ly6chi monocytes to sites of acute inflammation. Myeloid deficiency of Bmal1 also worsens chronic inflammation in diet-induced obesity. We studied whether myeloid Bmal1 deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesions. By generating Bmal1FloxP/FloxP;LysMCre mice on the Apoe-/- background, we showed that Bmal1 deletion in myeloid cells increased the size of atherosclerotic lesions. Bmal1 deficiency in monocytes and macrophages resulted in an increased total number of lesional macrophages in general and Ly6chi infiltrating monocyte-macrophages in particular, accompanied by skewed M2 to M1 macrophage phenotype. Ly6chi and/or Ly6clo monocyte subsets in blood, spleen, and bone marrow were not altered. Cell tracking and adoptive transfer of Ly6chi monocytes showed Bmal1 deficiency induced more trafficking of Ly6chi monocytes to atherosclerotic lesions, preferential differentiation of Ly6chi monocytes into M1 macrophages, and increased macrophage content and lesion size in the carotid arteries. We demonstrated that Bmal1 deficiency in macrophages promotes atherosclerosis by enhancing recruitment of Ly6chi monocytes to atherosclerotic lesions.-Huo, M., Huang, Y., Qu, D., Zhang, H., Wong, W. T., Chawla, A., Huang, Y., Tian, X. Y. Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis.

KEYWORDS:

chronic inflammation; macrophage; molecular clock

PMID:
27927724
PMCID:
PMC6191064
DOI:
10.1096/fj.201601030R
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center