TY - JOUR
T1 - Myeloid I kappa B alpha Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques
AU - Goossens, Pieter
AU - Vergouwe, Monique N.
AU - Gijbels, Marion J. J.
AU - Curfs, Danielle M. J.
AU - van Woezik, Johannes H. G.
AU - Hoeksema, Marten A.
AU - Xanthouleas, Sofia
AU - Leenen, Pieter J. M.
AU - Rupec, Rudolf A.
AU - Hofker, Marten H.
AU - de Winther, Menno P. J.
PY - 2011/7/21
Y1 - 2011/7/21
N2 - Activation of the transcription factor NF-kappa B appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kappa B inhibitor I kappa B alpha in atherosclerosis. Myeloid-specific deletion of I kappa B alpha 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 I kappa B alpha-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 I kappa B alpha(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 I kappa B alpha(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that I kappa B alpha deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques.
AB - Activation of the transcription factor NF-kappa B appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kappa B inhibitor I kappa B alpha in atherosclerosis. Myeloid-specific deletion of I kappa B alpha 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 I kappa B alpha-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 I kappa B alpha(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 I kappa B alpha(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that I kappa B alpha deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques.
U2 - 10.1371/journal.pone.0022327
DO - 10.1371/journal.pone.0022327
M3 - Article
C2 - 21814576
SN - 1932-6203
VL - 6
SP - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 7
ER -