University of Groningen Myeloid I kappa B alpha Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques

Activation of the transcription factor NF-kB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kB inhibitor IkBa in atherosclerosis. Myeloid-specific deletion of IkBa 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 IkBa-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 IkBa 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 IkBa mice more leukocytes are attracted to the plaques. In conclusion, we show that IkBa deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques. Citation: Goossens P, Vergouwe MN, Gijbels MJJ, Curfs DMJ, van Woezik JHG, et al. (2011) Myeloid IkBa Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques. PLoS ONE 6(7): e22327. doi:10.1371/journal.pone.0022327 Editor: Jaswinder K. Sethi, University of Cambridge, United Kingdom Received January 21, 2011; Accepted June 26, 2011; Published July 21, 2011 Copyright: 2011 Goossens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the Netherlands Heart Foundation (grant no. 2005B175), Netherlands Organization for Scientific Research (ZonMW VIDI 917-66-329 to MPJdW), the European Union (Marie-Curie MEST-CT-2005-020706/CADRE2 to PG) and the European Vascular Genomics Network (EVGN). MPJdW is an established investigator of the Netherlands Heart Foundation (2007T067 and 2009T034). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: dewinther@maastrichtuniversity.nl

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