Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines Validation Using a Novel Monocyte Chemoattractant Protein Monoclonal Antibody

Background— Pathological aspects of atherosclerosis are well described, but gene profiles during atherosclerotic plaque progression are largely unidentified. Methods and Results— Microarray analysis was performed on mRNA of aortic arches of ApoE−/− mice fed normal chow (NC group) or Western-type diet (WD group) for 3, 4.5, and 6 months. Of 10 176 reporters, 387 were differentially (>2×) expressed in at least 1 group compared with a common reference (ApoE−/−, 3- month NC group). The number of differentially expressed genes increased during plaque progression. Time-related expression clustering and functional grouping of differentially expressed genes suggested important functions for genes involved in inflammation (especially the small inducible cytokines monocyte chemoattractant protein [MCP]-1, MCP-5, macrophage inflammatory protein [MIP]-1α, MIP-1β, MIP-2, and fractalkine) and matrix degradation (cathepsin-S, matrix metalloproteinase-2/12). Validation experiments focused on the gene cluster of small ind...