Project description:This SuperSeries is composed of the following subset Series: GSE20680: Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease from the Cathgen Registry GSE20681: Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease from the PREDICT Trial Refer to individual Series
Project description:Background: Collateral artery growth, also termed arteriogenesis, occurs upon narrowing or occlusion of a major artery. To date, attempts to stimulate arteriogenesis in patients for therapeutic purposes have not been successful. Experimental models showed that circulating cells orchestrate arteriogenesis. In humans, a large heterogeneity exists in the arteriogenic response. We hypothesized that good arteriogenic responders (GARs) and bad arteriogenic responders (BARs) differ in gene expression profiles of circulating cells, thereby disclosing potential new therapeutic strategies for the stimulation of arteriogenesis. Methods: A total of 45 patients scheduled for percutaneous coronary intervention (PCI) for single-vessel coronary artery disease underwent intracoronary measurements of collateral flow index (CFI) to distinguish between GARs (CFI>0.21) and BARs (CFI≤0.21). Monocytes and CD34+ stem cells were collected from peripheral blood. A fraction of monocytes was further processed to obtain stimulated monocytes and macrophages. Whole genome transcriptome analysis was performed on all four cell types. Results: LPS-stimulated monocytes showed 244 genes differentially expressed (false discovery rate < 0.05) between GARs and BARs. Macrophage gene expression correlated with stimulated monocytes, while resting monocytes and stem cells revealed no differential gene expression. Stimulated monocytes from GARs showed a strongly attenuated response in several interferon- and apoptosis-related genes, which was corroborated at the protein level. Conclusions Circulating cells from GARs and BARs distinctively differ in their gene expression profiles upon stimulation. The reduced expression of interferon and apoptosis genes in GARs may lead to novel therapeutic approaches for the stimulation of collateral artery growth. Keywords: disease state analysis, stress response analysis, natural defense mechanism analysis
Project description:using peripheral blood monocytes to identify marker genes for an extensively grown coronary collateral circulation. We used microarrays to detail the global programme of gene expression underlying collateralization and identified distinct classes of differently regulated genes during this process. Experiment Overall Design: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire, a group of patients with coronary artery disease CAD and a group without CAD were selected for peripheral monocyte isolation, RNA extraction and hybridization on Affymetrix microarrays.
