RGD Reference Report - Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice. - Rat Genome Database

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Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice.

Authors: Veillard, NR  Kwak, B  Pelli, G  Mulhaupt, F  James, RW  Proudfoot, AE  Mach, F 
Citation: Veillard NR, etal., Circ Res. 2004 Feb 6;94(2):253-61. Epub 2003 Dec 1.
RGD ID: 4890030
Pubmed: PMID:14656931   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000109793.17591.4E   (Journal Full-text)

Increasing evidence supports the involvement of inflammation in the early phases of atherogenesis. Recruitment of leukocytes within the vascular wall, controlled by chemokines, is an essential process in the development of this common disease. In this study, we report that blocking a chemokine pathway in vivo with the CC chemokine antagonist Met-RANTES reduces the progression of atherosclerosis in a hypercholesterolemic mouse model. The reduction of lesions was correlated with a diminution of expression of several major chemokines and chemokine receptors, a decrease in leukocyte infiltration, and an increase of collagen-rich atheroma, features associated with stable atheroma. Treatment was well tolerated and serum lipid profiles were not affected. Whereas genetically engineered mice with deletion of either a CC chemokine or its receptor have demonstrated resistance to disease, to our knowledge, this is the first demonstration that treatment with a chemokine receptor antagonist limits the progression of atherosclerosis in vivo. Thus, our findings indicate that blockade of chemokine receptor/ligand interactions might become a novel therapeutic strategy to reduce the evolution of this common disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arteriosclerosis  ISOCcl5 (Mus musculus)4890030; 4890030 RGD 
arteriosclerosis  IMP 4890030 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Mus musculus)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Homo sapiens)
CCL5  (C-C motif chemokine ligand 5)


Additional Information