Antagonism of RANTES Receptors Reduces Atherosclerotic Plaque Formation in Mice

ABSTRACT—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 chemok...

Full description

Saved in:
Bibliographic Details
Published in:Circulation research 2004-02, Vol.94 (2), p.253-261
Main Authors: Veillard, Niels R, Kwak, Brenda, Pelli, Graziano, Mulhaupt, Flore, James, Richard W, Proudfoot, Amanda E.I, Mach, François
Format: Article
Language:English
Subjects:
Animals
Aorta - drug effects
Aorta - pathology
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
Arteriosclerosis - pathology
Arteriosclerosis - prevention & control
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
CCR5 Receptor Antagonists
Chemokine CCL5 - analogs & derivatives
Chemokine CCL5 - metabolism
Chemokine CCL5 - pharmacology
Chemokines - biosynthesis
Chemokines - genetics
Chemotaxis, Leukocyte - drug effects
Cholesterol, Dietary - toxicity
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
Receptors, CCR1
Receptors, CCR2
Receptors, CCR5 - physiology
Receptors, Chemokine - antagonists & inhibitors
Receptors, Chemokine - biosynthesis
Receptors, Chemokine - deficiency
Receptors, Chemokine - drug effects
Receptors, Chemokine - genetics
Receptors, Chemokine - physiology
Receptors, LDL - deficiency
RNA, Messenger - genetics
Vasculitis - pathology
Vasculitis - prevention & control
Vertebrates: cardiovascular system
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:ABSTRACT—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.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000109793.17591.4E