title: MyeloidBmal1deletion increases monocyte recruitment and worsens atherosclerosis.
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 Ly6chimonocytes to sites of acute inflammation. Myeloid deficiency ofBmal1also worsens chronic inflammation in diet-induced obesity. We studied whether myeloidBmal1deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesions. By generatingBmal1FloxP/FloxP;LysMCremice on the Apoe-/-background, we showed thatBmal1deletion in myeloid cells increased the size of atherosclerotic lesions.Bmal1deficiency in monocytes and macrophages resulted in an increased total number of lesional macrophages in general and Ly6chiinfiltrating monocyte-macrophages in particular, accompanied by skewed M2 to M1 macrophage phenotype. Ly6chiand/or Ly6clomonocyte subsets in blood, spleen, and bone marrow were not altered. Cell tracking and adoptive transfer of Ly6chimonocytes showedBmal1deficiency induced more trafficking of Ly6chimonocytes to atherosclerotic lesions, preferential differentiation of Ly6chimonocytes into M1 macrophages, and increased macrophage content and lesion size in the carotid arteries. We demonstrated thatBmal1deficiency in macrophages promotes atherosclerosis by enhancing recruitment of Ly6chimonocytes to atherosclerotic lesions.-Huo, M., Huang, Y., Qu, D., Zhang, H., Wong, W. T., Chawla, A., Huang, Y., Tian, X. Y. MyeloidBmal1deletion increases monocyte recruitment and worsens atherosclerosis.
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Huo
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Dan
authors.initials: D
authors.lastname: Qu
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.|Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong; xytian@cuhk.edu.hk.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.|School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D017353:Gene Deletion; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype
chemical_list: D056930:ARNTL Transcription Factors; D001057:Apolipoproteins E; C538961:Bmal1 protein, mouse
keywords: chronic inflammation; macrophage; molecular clock