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

• Published in: PloS one 2011, Vol.6 (7), p.e22327-e22327
• Main Authors: Goossens, Pieter, Vergouwe, Monique N, Gijbels, Marion J J, Curfs, Danielle M J, van Woezik, Johannes H G, Hoeksema, Marten A, Xanthoulea, Sofia, Leenen, Pieter J M, Rupec, Rudolf A, Hofker, Marten H, de Winther, Menno P J
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins; Apolipoproteins E - metabolism; Arteriosclerosis; Atherogenesis; Atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Biology; Blotting, Western; Bone marrow; Bone Marrow Transplantation; Cell activation; Cell Adhesion; Chemokines; Clonal deletion; Cytokines; Endothelial cells; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Female; Free radicals; Gene expression; Genotype & phenotype; I-kappa B Proteins - physiology; Immunoenzyme Techniques; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammatory diseases; Kinases; Lesions; Leukocytes; Leukocytes - metabolism; Leukocytes - pathology; Lipoproteins; Low density lipoprotein; Macrophages; Macrophages - metabolism; Macrophages - pathology; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - pathology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB protein; Pathogens; Plaques; Receptors, LDL - physiology; Recruitment; Stem cell transplantation; Studies; Transcription activation; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022327

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.