Scientific publications

CCL20 Is Increased in Hypercholesterolemic Subjects and Is Upregulated By LDL in Vascular Smooth Muscle Cells: Role of NF-{kappa}B

Calvayrac O, Rodríguez-Calvo R, Alonso J, Orbe J, Martín-Ventura JL, Guadall A, Gentile M, Juan-Babot O, Egido J, Beloqui O, Paramo JA, Rodríguez C, Martínez-González J.
Centro de Investigación Cardiovascular, Consejo Superior de Investigaciones Científicas, Institut Català de Ciències Cardiovasculars, Instituto de Investigaciones Biomédicas Sant Pau, Barcelona, Spain; Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain; Vascular Research Laboratory, Fundación Jiménez Diaz-Autonoma University, Madrid, Spain; Department of Internal Medicine University Clinic, School of Medicine, University of Navarra, Pamplona, Spain.

Magazine: Arteriosclerosis, Thrombosis and Vascular Biology

Date: Aug 18, 2011

Hematología y Hemoterapia [SP] Unidad de Chequeos [SP]

Our aim was to analyze the regulation of CC Chemokine ligand 20 (CCL20) by LDL in human vascular smooth muscle cells (VSMC).

In asymptomatic subjects, circulating CCL20 levels were higher in patients with hypercholesterolemia (18.5±3.2 versus 9.1±1.3 pg/mL; P<0.01). LDL induced the expression of CCL20 in VSMC in a dose- and time-dependent manner. Increased levels of CCL20 secreted by LDL-treated VSMC significantly induced human lymphocyte migration, an effect reduced by CCL20 silencing.

The upregulation of CCL20 by LDL was dependent on the activation of kinase signaling pathways and NF-κB. By site-directed mutagenesis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we identified a NF-κB site (-80/-71) in CCL20 promoter critical for LDL responsiveness. Lysophosphatidic acid mimicked the upregulation of CCL20 induced by LDL, and minimal oxidation of LDL increased the ability of LDL to induce CCL20 through a mechanism that involves lysophosphatidic acid receptors. CCL20 was overexpressed in atherosclerotic lesions from coronary artery patients, colocalizing with VSMC. CCL20 was detected in conditioned media from healthy human aorta and its levels were significantly higher in secretomes from carotid endarterectomy specimens.

This study identifies CCL20 in atherosclerotic lesions and recognizes this chemokine as a mediator highly sensitive to the inflammatory response elicited by LDL.

CITATION  Arterioscler Thromb Vasc Biol. 2011 Aug 18



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