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Gene Expression In Human Aneurysm Versus Occlusive Aortic Tissue

James R. Elmore, David P. Franklin, Spencer W. Galt, David J. Carey ∙ Geisinger Medical Center, Danville, PA

OBJECTIVES: The goal was to use microarray expression profiling to compare gene expression in abdominal aortic aneurysm (AAA), aortic occlusive disease (AOD), and normal abdominal aorta.
METHODS: RNA from human AAA, AOD and normal abdominal aorta (n=4 each) was used for gene expression profiling on Affymetrix U-133A Human Gene-Chip arrays (>22,000 probes). Genes with significant differences in expression (P < .05 by analysis of variance) were analyzed by hierarchical clustering analysis. Microarray data for genes of interest was validated by real time PCR assays.
RESULTS: 194 genes were significantly upregulated in both AAA and AOD compared to normal tissue. 127 genes were upregulated only in AAA and 97 genes were upregulated only in AOD. A large number of the upregulated genes (one-third) have known inflammatory or immune functions. The AAA specific genes were enriched in products with T cell-related functions. Other AAA specific inflammatory gene products were involved with interferon-γ, interleukin, and tumor necrosis factor signaling. The table shows a partial list of upregulated genes. MMP-9, which is implicated in tissue remodeling, was upregulated in both AAA and AOD by real time PCR.
CONCLUSIONS: AAA and AOD show increased expression of common genes, including many with inflammatory function, consistent with the known role of inflammation in these diseases. There are also genes with distinct AAA or AOD-specific expression, revealing a specific molecular basis for AAA and AOD. Upregulation of T cell and interferon-χ related genes in AAA is consistent with previous animal model data, and suggests critical roles for them in human AAA. This information provides new insights into the pathophysiology of these diseases. The ultimate outcome of this research will be to develop novel therapies and new tools for diagnosis of AAA and AOD.