Myeloid IκBα deficiency promotes atherogenesis by enhancing leukocyte recruitment to the plaques

PLoS One. 2011;6(7):e22327. doi: 10.1371/journal.pone.0022327. Epub 2011 Jul 21.

Abstract

Activation of the transcription factor NF-κB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-κB inhibitor IκBα in atherosclerosis. Myeloid-specific deletion of IκBα results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that IκBα-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that IκBα(del) mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in IκBα(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that IκBα deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / metabolism
  • Atherosclerosis / etiology*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Blotting, Western
  • Bone Marrow Transplantation
  • Cell Adhesion
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Female
  • I-kappa B Proteins / physiology*
  • Immunoenzyme Techniques
  • Inflammation / metabolism
  • Inflammation / pathology
  • Leukocytes / metabolism
  • Leukocytes / pathology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Receptors, LDL / physiology*

Substances

  • Apolipoproteins E
  • I-kappa B Proteins
  • NF-kappa B
  • Nfkbia protein, mouse
  • Receptors, LDL
  • NF-KappaB Inhibitor alpha