Abstract 202: Enrichment of Transcription Factor Binding Sites in the Promoter Regions of Differentially Expressed Genes in Vascular Smooth Muscle Cells from Abdominal Aortic Aneuryms.
Background We have previously shown that VSMC from AAA are unique compared to cells from normal aorta (NAA) and carotid endarterectomy (CEA) with increased production of matrix metalloproteinases and elastin degrading activity. The purpose of this study was to explore the mechanisms behind this phenotype.
Methods Tissue for VSMC cultures was obtained from patients undergoing AAA repair and CEA. NAA tissue was obtained from renal transplant patients (NAA). Total RNA was isolated from VSMC and subjected to whole-genome microarray. Enrichment of binding sites for transcription factors (TF) within 5 kD of transcription start sites of upregulated genes were identified using Whole Genome rVista. Enriched gene ontology terms were identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID).
Results Gene profiles of 22 AAA, 29 CEA, and 17 NAA cell lines were compared. We identified 120 upregulated genes in AAA-VSMC relative to NAA and CEA-VSMC (FDR<0.05). Analysis of transcription factor binding sites of these genes showed enrichment of TFs including members of the ETS, AP-1, and Rel/Ankyrin families. Gene ontology (GO) revealed enrichment of developmental process and immune system genes. Analysis by cell compartment showed enrichment of extracellular matrix and intermediate filament cytoskeleton genes (Table 1).
Conclusion This is the first study to demonstrates enrichment of TF families such as ETS, AP-1 and Rel-Ankyrin in AAA VSMC. This suggests that VSMC in AAA may not just be responding to inflammatory or other local stimuli, but may be directly contributing to the ECM changes that define AAA.
- © 2013 by American Heart Association, Inc.