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FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells

Min Zhu1, Qing-Jun Zhang, Lin Wang

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Atherosclerosis
|October 19, 2011
PubMed
Abstract

Insights

FoxO4 deficiency in bone marrow cells exacerbates atherosclerosis by increasing inflammation and oxidative stress. This study reveals FoxO4

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Immunology

Background:

  • FoxO proteins regulate critical cellular functions like immune homeostasis and oxidative stress response.
  • Their role in atherosclerosis development remains largely unexplored.
  • FoxO4 is a key member of the FoxO family.

Purpose of the Study:

  • To investigate the role of FoxO4 inactivation in promoting atherosclerosis.
  • To determine if FoxO4 deficiency in vivo impacts atherosclerotic plaque development.

Main Methods:

  • Crossbreeding apolipoprotein E-deficient (apoE(-/-)) mice with Foxo4-deficient (Foxo4(-/-)) mice.
  • High-fat diet (HFD) induction and analysis of atherosclerotic lesions.
  • Bone marrow transplantation experiments in chimeric mice.
  • In vitro studies on macrophage inflammatory responses and reactive oxygen species (ROS) production.

Main Results:

  • Foxo4(-/-)apoE(-/-) mice exhibited significantly elevated atherosclerosis compared to apoE(-/-) controls after HFD.
  • Increased macrophage and T cell infiltration was observed in atherosclerotic plaques of Foxo4-deficient mice.
  • Foxo4-deficient bone marrow cells promoted atherosclerosis, and Foxo4-null macrophages showed heightened IL-6 and ROS production in vitro.
  • Serum IL-6 levels were upregulated in HFD-fed Foxo4(-/-)apoE(-/-) mice.

Conclusions:

  • FoxO4 acts as an inhibitor of atherosclerosis development.
  • Its inhibitory effect is mediated through bone marrow-derived cells.
  • FoxO4 may suppress atherosclerosis by reducing ROS and inflammatory cytokines, thereby limiting monocyte recruitment and retention.

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