Chemokine receptor CCR1 disruption in bone marrow cells enhances atherosclerotic lesion development and inflammation in mice |
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Authors: | Potteaux Stéphane Combadière Christophe Esposito Bruno Casanova Saveria Merval Régine Ardouin Patrice Gao Ji-Liang Murphy Philip M Tedgui Alain Mallat Ziad |
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Institution: | Institut National de la Santé et de la Recherche Médicale, INSERM U689, H?pital Lariboisière, Paris, France. |
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Abstract: | Several chemokines or chemokine receptors are involved in atherogenesis. CCR1 is expressed by macrophages and lymphocytes, two major cell types involved in the progression of atherosclerosis, and binds to lesion-expressed ligands. We examined the direct role of the blood-borne chemokine receptor CCR1 in atherosclerosis by transplanting bone marrow cells from either CCR1+/+ or CCR1-/- mice into low-density lipoprotein-receptor (LDLr)-deficient mice. After exposure to an atherogenic diet for 8 weeks, no differences in fatty streak size or composition were detected between the 2 groups. After 12 weeks of atherogenic diet, however, an unexpected 70% increase in atherosclerotic lesion size in the thoracic aorta was detected in the CCR1-/- mice, accompanied by a 37% increase in the aortic sinus lesion area. CCR1-/- mice showed enhanced basal and concanavalin A-stimulated IFN-gamma production by spleen T cells and enhanced plaque inflammation. In conclusion, blood-borne CCR1 alters the immuno-inflammatory response in atherosclerosis and prevents excessive plaque growth and inflammation. |
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