Similarities and differences in the transcriptome of human atherosclerotic and non-atherosclerotic macrophages

Phenotypic and functional diversity between macrophage subpopulations reflects their plasticity to respond to microenvironmental signals. Apart from detecting differences in expression profiles, the comparison of the transcriptomes of different macrophage populations may also allow the definition of molecular similarities between these subsets. Transcriptome analysis of human Kuppfer cells, alveolar, splenic and atherosclerotic plaque residing macrophages using microarrays, identified 42 genes that are specifically expressed in atherosclerotic plaque macrophages. We also focus on the similarities in the transcriptome of human Kupffer cells, alveolar, splenic and atherosclerotic plaque residing macrophages. We hypothesized that these macrophages share a common expression signature. We performed microarray analysis on mRNA from these macrophage subsets (n = 4 patients) and developed a novel statistical method to identify genes with significantly similar expression levels. This method calculates the maximum difference in expression level of a gene, based on the estimated confidence interval on that genes expression variance. We listed the genes by equivalence ranking relative to their expression level. False Discovery Rate (FDR) estimation was used to determine significance. We identified 500 genes that had significantly equivalent expression levels in the macrophage subsets at an 5.5% FDR using a 90% confidence interval. Equivalently expressed genes, identified by this newly developed method, may not only help to dissect common molecular mechanisms, but also to identify cell or condition specific sets of marker genes that can be used for drug targeting and molecular imaging. Macrophages were isolated from N=4 tissues, being atherosclerotic plaques from carotid artery (CA), and from three none-atherosclerotic tissues, being lung (LU), spleen (SP), and liver (LI). This was done within four individual patients, defined as 275, 282, 288 and 289. Each of the N=16 biological samples was hybridized in duplicate against a common reference RNA, resulting in a total of N=16 microarray hybridizations.