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Circulating microRNAs in patients with aneurysmal dilatation of coronary arteries

ABSTRACT: To understand the mechanism of coronary artery aneurysmal dilatation, we identified and compared the expression of circulating miRNAs in three groups of patients. Group 1 enrolled patients with aneurysmal dilatation of coronary arteries (n = 20), Group 2 included patients with angiographically confirmed coronary artery disease (CAD), whereas Group 3 included 20 patients with normal coronary arteries. The miRNAs were isolated from plasma and profiled using PCR arrays miRCURY LNA Serum/Plasma Focus PCR Panels. We demonstrated that the plasma miRNAs levels were significantly different in Group 1 in collation with Group 2 and Group 3 (fold change > 2 and p < 0.05). The comparison of Group 1 with Group 3 identified twenty-one significantly up-regulated and two down-regulated miRNAs in patients with aneurysmal coronary artery dilatation compared to the control groups. Moreover, we identified six up-regulated and two down-regulated miRNAs in patients with CAD compared to the controls. The third comparison revealed four up-regulated and three down-regulated miRNAs in Group 1, when compared to CAD patients. In conclusion, this study demonstrates the specific signature of plasma miRNA, namely up-regulated and down-regulated, in patients with abnormal dilatation of coronary arteries and the comparison between the groups consisting of atherosclerotic and control patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198885 | GEO | 2022/03/18

REPOSITORIES: GEO

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:Objectives: To analyze the gene expression profile of peripheral blood monocytes in different stages of coronary artery disease (CAD) by transcriptome sequencing, and to explore potential genes and pathway involved in CAD pathogenesis. Methods: According to the screening of coronary angiography and quality control of blood samples, 8 intermediate coronary lesion patients were selected, then 8 patients with acute myocardial infarction and 8 patients with normal coronary angiography were matched by age and gender. Transcriptomics sequencing was conducted for the peripheral blood monocytes of these 24 samples by using Illumina HiSeq high-throughput platform. Then differentially expressed genes (DEGs) were analyzed. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and protein-protein interaction (PPI) network were applied to annotate the potential functions of DEGs. Results: Compared with the normal coronary angiography group, we identified a total of 169 DEGs in the intermediate coronary lesion group, which were significantly enriched in 59 GO terms and 17 KEGG pathways. Compared with the normal coronary angiography group, we found a total of 2028 DEGs, which were significantly enriched in 311 GO terms and 20 KEGG pathways in the acute myocardial infarction group. The cross-comparison between normal versus intermediate coronary lesion group, and normal versus acute myocardial infarction group included 98 differential genes with 65 up regulated and 33 down regulated genes, which were significantly enriched in 46 GO terms and 10 KEGG pathways. During the progression of CAD, there was a significant up-regulated expression of CSF3、IL-1A、CCR7 and IL-18, and down-regulated expression of MAPK14. Besides GO items such as inflammatory response was significantly enriched, KEGG analysis showed the most remarkable enrichments in IL-17 signaling pathway and cytokine-cytokine receptor interactions. Conclusions: Transcriptomics profiles vary in patients with different severity of CAD. CSF3、IL-1A、CCR7、IL-18 and MAPK14, as well as IL-17 signaling pathway and cytokines and cytokine receptor interaction signaling pathway related with inflammatory response might be the potential biomarker and targets for the treatment of coronary artery disease.

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Circulating microRNAs in patients with aneurysmal dilatation of coronary arteries

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