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.

A retrospective comparison of thrombectomy followed by stenting and thrombectomy alone for the management of deep vein thrombosis with May-Thurner syndrome.

OBJECTIVE: To summarize the clinical results of thrombectomy with stenting (TBS) in patients with deep venous thrombosis (DVT) secondary to May-Thurner syndrome (MTS) compared with the outcomes in patients treated with thrombectomy alone (TB). METHODS: A retrospective observation of patients with proximal DVT secondary to MTS was conducted in our institution. Patients accepted treatment including either catheter-directed TBS or TB. The complications and stent patency rates were recorded after treatments. The clinical results were assessed in both groups. The independent predictors for in-stent restenosis were further calculated in this study. RESULTS: We included 372 patients with DVT secondary to MTS. Two hundred twenty-one patients received treatment with thrombectomy with TBS and 151 with TB. A longer mean procedure time (65.1 ± 13.9 minutes vs 49.5 ± 15.7 minutes; P < .001) and higher venous perforation rate (23 patients vs 5 patients; P = .011) were observed in the TBS group than in the TB group. The median follow-up time was 34 months. The patency rates in the TBS group at 36 months were as follows: primary patency rate of 74.0% and secondary patency rate of 92.1%. Independent predictors for restenosis included visible remaining collateral vessels (hazard ratio [HR], 1.12-3.29; P = .02), residual thrombus (HR, 1.40-4.38; P = .002), and tapered iliac vein (HR, 1.26-4.06; P = .006). Clinical results, including Venous Clinical Severity Scores (TBS, 8.0 ± 3.0; TB, 11.4 ± 3.2), Chronic Venous Insufficiency Questionnaire score (TBS, 76.4 ± 4.0; TB, 83.1 ± 4.6), Villalta scores (TBS, 3.8 ± 1.7; TB, 6.6 ± 3.2), and edema scores (TBS, 0.7 ± 0.7; TB, 1.6 ± 0.6), improved significantly in the TBS group. CONCLUSIONS: TBS is effective and feasible for patients with proximal DVT secondary to MTS. Furthermore, compared with TB, additional stenting might be effective in improving the venous clinical results at follow-up observations.

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.

miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis.

BACKGROUND: Deep venous thrombosis (DVT) of lower extremities is a common thrombotic disease, occurring either in isolation or as a complication of other diseases or procedures. MiR-21 is one of important microRNAs which play critical role in various cellular function. This study aim to determine the effect of miR-21 on endothelial progenitor cells (EPCs) and its role in predicting prognosis of DVT. METHODS: EPCs was isolated from DVT models and control subjects. miR-21 expression was confirmed by RT-PCR. Potential target mRNA was predicted by bioinformatics analysis. EPCs biological functions were examined by CCK-8 and tube formation assay. Besides, miR-21 expression was determined in DVT patients to investigate the correlation between miR-21 expression and prognosis of DVT. Cox proportional hazard regression analyses were also performed to reveal the risk factors associated with prognosis. RESULTS: Here, we found miR-21 was downregulated in EPCs of DVT model rats. Increased miR-21 expression promoted proliferation and angiogenesis of EPCs. Moreover, we demonstrated that FASLG was a target of miR-21 and revealed that FASLG knockdown inhibited function of EPCs. Upregulation of miR-21 led to thrombus resolution in a rat model of venous thrombosis. In addition, lower expression level of miR-21 in DVT patients was associated with an increase of recurrent DVT and post thrombotic syndrome (PTS). Furthermore, Cox proportional hazard regression analyses demonstrated miR-21 expression level as an independent predictor of recurrence of DVT. CONCLUSIONS: Our data revealed a role of miR-21 in regulating biological function of EPCs and could be a predictor for recurrent DVT or PTS.