MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease.

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.

Identification of key genes related to heart failure by analysis of expression profiles.

Introduction: To elucidate the candidate biomarkers involved in the pathogenesis process of heart failure (HF) via analysis of differentially expressed genes (DEGs) of the dataset from the Gene Expression Omnibus (GEO). Material and methods: The GSE76701 gene expression profiles regarding the HF and control subjects were respectively analysed. Briefly, DEGs were firstly identified and subjected to Cytoscape plug-in ClueGO + CluePedia and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was then built to analyse the interaction between DEGs, followed by the construction of an interaction network by combining with hub genes with the targeted miRNA genes of DEGs to identify the key molecules of HF. In addition, potential drugs targeting key DEGs were sought using the drug-gene interaction database (DGIdb), and a drug-mRNA-miRNA interaction network was also constructed. Results: A total of 489 DEGs were verified between HF and control, which mainly enriched in type I interferon and leukocyte migration according to molecular function. Significantly increased levels of GAPDH, GALM1, MMP9, CCL5, and GNAL2 were found in the HF setting and were identified as the hub genes based on the PPI network. Furthermore, according to the drug-mRNA-miRNA network, FCGR2B, CCND1, and NF-κb, as well as corresponding miRNA-605-5p, miRNA-147a, and miRNA-671-5p were identified as the drug targets of HF. Conclusions: The hub genes GAPDH, GALM1, MMP9, CCL5, and GNAL2 were significantly increased in HF. miRNA-605-5p, miRNA-147a, and miRNA-671-5p were predicted as the drug target-interacted gene-miRNA of HF.

Berberine Protects Against Simulated Ischemia/Reperfusion Injury-Induced H9C2 Cardiomyocytes Apoptosis In Vitro and Myocardial Ischemia/Reperfusion-Induced Apoptosis In Vivo by Regulating the Mitophagy-Mediated HIF-1α/BNIP3 Pathway.

Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (ΔΨm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1α to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1α/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.