Identification of 5 hub genes for diagnosis of coronary artery disease.

Background: Coronary artery disease (CAD) is a main cause leading to increasing mortality of cardiovascular disease (CVD) worldwide. We aimed to discover marker genes and develop a diagnostic model for CAD. Methods: CAD-related target genes were searched from DisGeNET. Count expression data and clinical information were screened from the GSE202626 dataset. edgeR package identified differentially expressed genes (DEGs). Using online STRING tool and Cytoscape, protein-protein reactions (PPI) were predicted. WebGestaltR package was employed to functional enrichment analysis. We used Metascape to conduct module-based network analysis. VarElect algorithm provided genes-phenotype correlation analysis. Immune infiltration was assessed by ESTIMATE package and ssGSEA analysis. mRNAsi was determined by one class logistic regression (OCLR). A diagnostic model was constructed by SVM algorithm. Results: 162 target genes were screened by intersection 1,714 DEGs and 1,708 CAD related target genes. 137 target genes of the 162 target genes were obtained using PPI analysis, in which those targets were enriched in inflammatory cytokine pathways, such as chemokine signaling pathway, and IL-17 signaling pathway. From the above 137 target genes, four functional modules (MCODE1-4) were extracted. From the 162 potential targets, CAD phenotype were directly and indirectly associated with 161 genes and 22 genes, respectively. Finally, 5 hub genes (CCL2, PTGS2, NLRP3, VEGFA, LTA) were screened by intersections with the top 20, directly and indirectly, and genes in MCODE1. PTGS2, NLRP3 and VEGFA were positively, while LTA was negatively correlated with immune cells scores. PTGS2, NLRP3 and VEGFA were negatively, while LTA was positively correlated with mRNAsi. A diagnostic model was successfully established, evidenced by 92.59% sensitivity and AUC was 0.9230 in the GSE202625 dataset and 94.11% sensitivity and AUC was 0.9706 in GSE120774 dataset. Conclusion: In this work, we identified 5 hub genes, which may be associated with CAD development.

miR-22-3p Suppresses Endothelial Progenitor Cell Proliferation and Migration via Inhibiting Onecut 1 (OC1)/Vascular Endothelial Growth Factor A (VEGFA) Signaling Pathway and Its Clinical Significance in Venous Thrombosis.

BACKGROUND Proliferation and migration play crucial roles in various physiological processes, especially in injured endothelial repair. Endothelial progenitor cells (EPCs), as the precursors of endothelial cell, are involved in the regeneration of the endothelial lining of blood vessels. Furthermore, EPCs were found to be a potential choice for venous thrombosis (VT) treatment. MATERIAL AND METHODS EPCs were isolated from human peripheral blood of healthy adults and VT patients. Differently expressed micro(mi)RNAs were examined by quantitative real-time polymerase chain reaction, after which proliferative capacity and migration effect were tested by Cell-Counting Kit 8, scratch wound assay, and transwell assays. Bioinformatic analysis was applied to investigate the potential target messenger ribonucleic acid and a dual-luciferase reporting system was utilized to confirm the binding of miR-22-3p to its target gene. Western blot was carried out to detect candidate protein expression level. Finally, miR-22-3p expression was monitored in VT patients during follow-up to assess its correlation with prognosis of VT. RESULTS Our data revealed that miR-22-3p was upregulated in EPCs derived from deep VT (DVT) individuals and suppression of miR-22-3p contributed to proliferation and migration of EPCs. In addition, miR-22-3p/onecut 1 (OC1)/vascular endothelial growth factor A (VEGFA) signaling pathway was involved in regulating EPC migration and proliferation. In addition, lower expression of miR-22-3p in DVT patients indicated decreased risk of VT recurrence. CONCLUSIONS Our results suggest that miR-22-3p regulates OC1/VEGFA signaling and is involved in regulating EPC proliferation and migration. The expression level of miR-22-3p could be monitored to predict DVT patients' prognosis.

Effectiveness of catheter directed thrombolysis and stent implantation on iliofemoral vein thrombosis caused by iliac vein compression.

The purpose of this study was to objectively assess the morbidity of post-thrombotic syndrome (PTS) in iliofemoral vein thrombosis treated with catheter-directed thrombolysis (CDT) and stenting under the protection of inferior vena cava (IVC) filter. All patients with an unprovoked episode of iliofemoral vein thrombosis combined with iliac vein compression syndrome (IVCS) during January 2011 and January 2015 were enrolled. Clinical records of all patients were evaluated. Firstly, cox regression was performed to find out the factors impacted the incidence of PTS. Then, Kaplan Meier analysis was conducted to verify the roles of these factors in PTS. A total of 247 patients who underwent CDT and IVC filter insertion for iliofemoral vein thrombosis and were found stenosis in the iliac vein after CDT were included in this study. Among them, 74 patients suffered PTS diagnosed via Villalta scale. Comparison with patients without stent implantation and filter withdrawal, patients with stent implantation and filter withdrawal had a less risk of PTS, but patients with a lesion in the left or bilateral proximal deep vein had a more risk of PTS. Cox regression found that stent implantation was a preventive measure to prevent PTS (OR 0.541, 95% CI 0.334-0.876, p = 0.012). The Kaplan-Meier curve found that patients with stent implantation had a less ratio of PTS occurrence (P = 0.008). In patients with iliofemoral vein thrombosis and IVCS, stent implantation to solve the residual obstruction after CDT might play an important role in preventing PTS.

Differential co-expression analysis of venous thromboembolism based on gene expression profile data.

The aim of the present study was to screen differentially co-expressed genes and the involved transcription factors (TFs) and microRNAs (miRNAs) in venous thromboembolism (VTE). Microarray data of GSE19151 were downloaded from Gene Expression Omnibus, including 70 patients with VTE and 63 healthy controls. Principal component analysis (PCA) was performed using R software. Differential co-expression analysis was performed using R, followed by screening of modules using Cytoscape. Functional annotation was performed using Database for Annotation, Visualization, and Integrated Discovery. Moreover, Fisher test was used to screen key TFs and miRNAs for the modules. PCA revealed the disease and healthy samples could not be distinguished at the gene expression level. A total of 4,796 upregulated differentially co-expressed genes (e.g. zinc finger protein 264, electron-transfer-flavoprotein, beta polypeptide and Janus kinase 2) and 3,629 downregulated differentially co-expressed genes (e.g. adenylate cyclase 7 and single-stranded DNA binding protein 2) were identified, which were further mined to obtain 17 and eight modules separately. Functional annotation revealed that the largest upregulated module was primarily associated with acetylation and the largest downregulated module was mainly involved in mitochondrion. Moreover, 48 TFs and 62 miRNA families were screened for the 17 upregulated modules, such as E2F transcription factor 4, miR-30 and miR-135 regulating the largest module. Conversely, 35 TFs and 18 miRNA families were identified for the 8 downregulated modules, including mitochondrial ribosomal protein S12 and miR-23 regulating the largest module. Differentially co-expressed genes regulated by TFs and miRNAs may jointly contribute to the abnormal acetylation and mitochondrion presentation in the progression of VTE.

The efficacy of percutaneous transluminal angioplasty treatment for the patients with arteriovenous fistula dysfunction.

BACKGROUND: The aim of this study was to evaluate the efficacy and outcomes of three different percutaneous transluminal angioplasty (PTA) approaches in the treatment of patients with arteriovenous fistula (AVF) dysfunction. METHODS: A retrospective review was performed in a total of 183 patients with AVF dysfunction treated with 3 different PTA approaches (transarterial, transvenous and combination) in our hospital from October 2006 to October 2012. Technical and clinical success rate, complications and vessel patency were assessed. RESULTS: The mean length of pretreatment stenosis segment was 2.0±1.4 cm (range 0.5-6.8 cm), and the mean length of stenosis segment was shortest in transvenous group. The technical success rates using transarterial and transvenous approach were 80.4% (P<0.01) and 87.8% (P<0.01), respectively, compared to 32.4% of combination approach. Moreover, the clinical success rates using transarterial and transvenous approach were 92.8% and 95.9% (P<0.01), respectively, comparing to 54.1% of combination approach. Moreover, significant difference was found on the presence of vasospasm among the three groups (P<0.01). In addition, a higher primary patency rate was also achieved by using transarterial (P<0.01) and transvenous approach (P<0.01) compared to combination approach. CONCLUSIONS: Transarterial and transvenous PTA is more efficient than combination PTA for the patients with dysfunctional AVF. A high technical and clinical success rate could be achieved by using both approaches. Limited number of complications and high rate of primary patency were found in the patients.