Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Mingyu Huo
  • Yuhong Huang
  • Dan Qu
  • Hongsong Zhang
  • Wing Tak Wong
  • Ajay Chawla
  • Xiao Yu Tian

Detail(s)

Original languageEnglish
Pages (from-to)1097-1106
Journal / PublicationFASEB Journal
Volume31
Issue number3
Publication statusPublished - 1 Mar 2017
Externally publishedYes

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.

Research Area(s)

  • Chronic inflammation, Macrophage, Molecular clock

Bibliographic Note

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Citation Format(s)

Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis. / Huo, Mingyu; Huang, Yuhong; Qu, Dan et al.
In: FASEB Journal, Vol. 31, No. 3, 01.03.2017, p. 1097-1106.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review