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Article Dans Une Revue Arteriosclerosis, Thrombosis, and Vascular Biology Année : 2011

CCL20 Is Increased in Hypercholesterolemic Subjects and Is Upregulated By LDL in Vascular Smooth Muscle Cells

Ricardo Rodríguez-Calvo
  • Fonction : Auteur
Judith Alonso
  • Fonction : Auteur
Josune Orbe
  • Fonction : Auteur
Jose Luis Martín-Ventura
  • Fonction : Auteur
Anna Guadall
  • Fonction : Auteur
Maurizio Gentile
  • Fonction : Auteur
Oriol Juan-Babot
  • Fonction : Auteur
Jesus Egido
  • Fonction : Auteur
Oscar Beloqui
  • Fonction : Auteur
José A Paramo
  • Fonction : Auteur
Cristina Rodríguez
  • Fonction : Auteur
José Martínez-González
  • Fonction : Auteur

Résumé

Objective-Our aim was to analyze the regulation of CC Chemokine ligand 20 (CCL20) by LDL in human vascular smooth muscle cells (VSMC). Methods and Results-In asymptomatic subjects, circulating CCL20 levels were higher in patients with hypercholesterolemia (18.5Ϯ3.2 versus 9.1Ϯ1.3 pg/mL; PϽ0.01). 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-B. By site-directed mutagenesis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we identified a NF-B site (Ϫ80/Ϫ71) 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. Conclusion-This study identifies CCL20 in atherosclerotic lesions and recognizes this chemokine as a mediator highly sensitive to the inflammatory response elicited by LDL.
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hal-03026087 , version 1 (26-11-2020)

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Olivier Calvayrac, Ricardo Rodríguez-Calvo, Judith Alonso, Josune Orbe, Jose Luis Martín-Ventura, et al.. CCL20 Is Increased in Hypercholesterolemic Subjects and Is Upregulated By LDL in Vascular Smooth Muscle Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 2011, 31 (11), pp.2733-2741. ⟨10.1161/ATVBAHA.111.235721⟩. ⟨hal-03026087⟩
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