FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells

Min Zhu, Qing Jun Zhang, Lin Wang, Hao Li, Zhi Ping Liu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objectives: FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis. Methods and results: Apolipoprotein E-deficient (apoE -/-) mice were crossbred with animals lacking Foxo4 (Foxo4 -/-). After 10 weeks on a high fat diet (HFD), Foxo4 -/-apoE -/- mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE -/- mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4 -/- bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4 -/-apoE -/- mice compared to those of apoE -/- mice. Conclusions: FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention.

Original languageEnglish (US)
Pages (from-to)492-498
Number of pages7
JournalAtherosclerosis
Volume219
Issue number2
DOIs
StatePublished - Dec 1 2011

Keywords

  • Bone marrow
  • FoxO
  • Inflammation
  • Macrophage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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