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:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis
Project description:Innate immune cells importantly contribute to the pathphysiology of atherosclerotic cardiovascular disease CVD. Previous studies show that isolated innate immune cells from patients with atherosclerotic CVD have an activated phenotype. To understand the origin of this immune cell activation, we performed bone marrow aspiration in 10 male patients with severe coronary artery disease (based on coronary CT angiography) and 10 control subjects in whom coronary atherosclerosis was excluded. After flow sorting of HSCs, MPPs, and GMPs, we performed RNAseq.
Project description:LncRNA expression profiling for 6 human monocytes samples from Coronary Artery Disease patients and non Coronary Artery Disease patients
Project description:LncRNA expression profiling for 6 human plasma samples from Coronary Artery Disease patients and non Coronary Artery Disease patients
Project description:Coronary artery disease (CAD) and peripheral artery disease (PAD) are prevalent atherosclerotic disorders that exhibit distinct clinical and pathological presentations. We used whole-blood RNA sequencing to investigate circulating transcriptomic differences between PAD and CAD. Whole-blood RNA sequencing was performed in 71 subjects 40-65 years of age with symptomatic PAD (n=20) or CAD (n=51). Patients with concomitant PAD and CAD were excluded. Differential expression analysis was performed to compare circulating gene expression in patients with PAD and patients with CAD. We identified 106 genes differentially expressed between PAD and CAD (p adj. < 0.1). Pathway analysis identified upregulation of interferon signaling pathways in CAD and upregulation of neutrophil degranulation and toll-like receptor signaling pathways in PAD. Cell type deconvolution revealed greater fractional abundance of T cell subsets in CAD compared to PAD. Patients with PAD had higher neutrophil-lymphocyte ratio that patients with CAD (3.4 vs. 2.3, p=0.01). In conclusion, PAD and CAD have unique circulating transcriptomes characterized by differences in inflammatory gene expression.
Project description:Biomarker discovery for coronary artery disease using circulating extracellular vesicles derived from plasma samples of ACS patients.