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Comprehensive analysis of RNA expression profiling in patients with multi- vs single-vessel coronary artery disease

ABSTRACT: Patients with multi-vessel coronary artery disease (MV-CAD) often exhibit poor clinical outcomes compared to single-vessel coronary artery disease (SV-CAD). Increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) may play a critical role in cardiovascular diseases, however their impact on various vessel lesions, is largely unknown. Here, six patients were selected for the SV-CAD group and 13 for the MV-CAD group by the number of diseased coronary branches. Total RNAs were extracted from peripheral blood of the patients, and the expression profiling was conducted by RNA sequencing (RNASeq). Differentially expressed mRNAs, miRNAs and lncRNAs were identified with p<0.05 and |log2 FC|>1. The GO and KEGG pathway enrichment analysis indicated that differentially expressed mRNAs were mainly enriched in Wnt, Ras and ErbB signaling pathways; miRNAs in mTOR and ErbB signaling pathways; lncRNAs in ErbB signaling pathway, fatty acid metabolism and platelet activation. In addition, we established the ceRNA network and revealed that lncRNA ENST00000501122 may competitively combine with miR-6724-5, regulating the expression of its target mRNAs. Lastly, the most significantly differentially expressed miRNAs, let-7b-5p, let-7e-5p and miR-190a-5p, were selected to evaluate their effects on lipid metabolism and inflammation in cell lines. Overall, our study provides a comprehensive analysis of the transcriptome between MV-CAD and SV-CAD, which will not only help us better understand the mechanisms of different CADs, but also provide a theoretical basis for the prevention and treatment of cardiovascular disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190627 | GEO | 2021/12/12

REPOSITORIES: GEO

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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.

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Comprehensive analysis of RNA expression profiling in patients with multi- vs single-vessel coronary artery disease

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