Expression of cytokine genes in the aorta is altered by the deficiency in MCP-1: effect of a high-fat, high-cholesterol diet.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) facilitates the recruitment of monocytes/macrophages into vascular intima, and it is probably involved in the regulation of other signaling pathways relevant to the pathogenesis of arteriosclerosis and metabolic disturbances. However, chemokines are redundant. Consequently, the protective effect of MCP-1 deficiency may be mediated by changes in other cytokine signals.


RESULTS
Changes in the pattern of gene expression in the aorta were evaluated in LDLr(-/-) and MCP-1(-/-) LDLr(-/-) mice fed either chow or Western-style diet. Functional analyses were used to characterize the pathways affected and to identify biological processes in which MCP-1 may play an additional role. Some data also suggest that MCP-5 may act as a surrogate for MCP-1 deletion. Arteriosclerosis lesion and plaque composition are associated with enrichment in the cytokine-cytokine receptor interaction pathway.


CONCLUSIONS
There is a complex network of interactions linking MCP-1 and other cytokines. The lack of MCP-1 limits the aortic response to atherogenic stimuli, but does not completely protect against neointima formation. Activation of alternative inflammatory pathways in the vascular wall in response to MCP-1 deficiency should be considered to fully understand the actual role of this chemokine.
Rull
Anna
A
Centre de Recerca Biomèdica, Hospital Universitari Sant Joan de Reus, IISPV-Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, c/Sant Joan s/n, Reus, Spain.
Beltrán-Debón
Raúl
R
Aragonès
Gerard
G
Rodríguez-Sanabria
Fernando
F
Alonso-Villaverde
Carlos
C
Camps
Jordi
J
Joven
Jorge
J
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology*; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011973:Receptors, LDL / Q000378:metabolism; D013997:Time Factors
D018932:Chemokine CCL2; D016207:Cytokines; D004041:Dietary Fats; D011973:Receptors, LDL; D002784:Cholesterol