Identification of an Epigenetic Signature for Coronary Heart Disease in Postmenopausal Women's PBMC DNA.

Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women's development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein-protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women's molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

Identification of Five Hub Genes Based on Single-Cell RNA Sequencing Data and Network Pharmacology in Patients With Acute Myocardial Infarction.

Acute myocardial infarction (AMI) has a high mortality. The single-cell RNA sequencing (scRNA-seq) method was used to analyze disease heterogeneity at the single-cell level. From the Gene Expression Omnibus (GEO) database (GSE180678), AMI scRNA-seq were downloaded and preprocessed by the Seurat package. Gene expression data came from GSE182923. Cell cluster analysis was conducted. Cell types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on hub genes. Drugs were predicted by protein-protein interaction (PPI) and molecular docking. In total, 7 cell clusters were defined based on the scRNA-seq dataset, and the clusters were labeled as 5 cell types by marker genes. Hematopoietic stem cell types as a differential subgroups were higher in AMI than in healthy tissues. From available databases and PPI analysis, 52 common genets were identified. Based on 52 genes, 5 clusters were obtained using the MCODE algorithm, and genes in these 5 clusters involved in immune and inflammatory pathways were determined. Correlation analysis showed that hematopoietic stem cell types were negatively correlated with ATM, CARM1, and CASP8 but positively correlated with CASP3 and PPARG. This was reversed with immune cells. Molecular docking analysis showed that DB05490 had the lowest docking score with PPARG. We identified 5 hub genes (ATM, CARM1, CASP8, CASP3, and PPARG) involved in AMI progression. Compound DB05490 was a potential inhibitor of PPAG.

Inhibition of Src improves cardiac fibrosis in AngII-induced hypertrophy by regulating the expression of galectin-3.

BACKGROUND: The expression of Src is upregulated in the vasculature associated with cardiac hypertrophy events. Here, we aimed to explore the underlying mechanism of Src in angiotensin II (AngII)-mediated cardiac fibrosis and hypertrophy. METHODS: The heart conditional Src knockout mouse model was established and administrated with AngII. The effects of Src on the AngII-mediated cardiac hypertrophy were assessed by Hematoxylin and Eosin (HE), Masson's trichrome, immunohistochemical staining, Annexin V-FITC/PI apoptosis detection assay and Western blot analysis. RESULTS: The expression levels of galectin-3, Src and the hypertrophy marker brain natriuretic peptide (BNP), as well as the phosphorylation of Src were all elevated in heart tissues of mice with AngII-induced cardiac hypertrophy and fibrosis. Heart conditional Src knockout attenuated AngII-activated cardiac fibrosis and hypertrophy in mice. Consistently, AngII could promote the expression of Src in a dose-dependent manner and the knockout of Src impaired Ang II-mediated apoptosis and fibrosis in the cardiomyocytes. In addition, Src inhibition suppressed the expression of galectin-3 in vivo and in vitro. Specifically, AngII could upregulate the expression of galectin-3, and knockdown of galectin-3 (Gal-3) remarkably inhibited AngII-enhanced apoptosis and fibrosis in the cardiomyocytes. Furthermore, overexpression of galectin-3 reinforced Ang II-induced cell apoptosis and fibrosis that was attenuated by knockout of Src. CONCLUSIONS: Our findings indicate that Src and Gal-3 play an important role in AngII-mediated cardiac structural remodeling. Src and galectin-3 might serve as potential targets for the treatment of AngII-induced cardiac fibrosis and hypertrophy.

The Protective Effect of miR-27-3p on Ischemia-Reperfusion-Induced Myocardial Injury Depends on HIF-1α and Galectin-3.

Cardiac ischemia-reperfusion injury usually results in acute myocardial infarction (AMI). MiRNAs have been identified as key regulators of AMI. This study was carried out to investigate the effect of miR-27-3p on cardiomyocyte injury in AMI. CCK-8 and flow cytometry assays were used to evaluate cell viability and apoptosis. The expression levels of miR-27-3p, galectin-3, and hypoxia-inducible factor-1α were measured by qRT-PCR. The relationship among miR-27-3p, galectin-3, and HIF-1α was assessed by bioinformatics analysis and luciferase assay. The effects of miR-27-3p and/or galectin-3 and HIF-1α on the inhibition of cell viability and apoptosis induced by H/R were explored. The expression levels of apoptosis-related proteins were determined by Western blot analysis. The expression levels of miR-27-3p were reduced in both ischemia-reperfusion myocardium and HL-1 cells during hypoxia. Overexpression of miR-27-3p reduced I/R-induced myocardial injury, and HIF-1α can reduce this effect. H/R reduced the expression levels of miR-27-3p in HL-1 cardiomyocytes, and HIF1-α reduced this effect, indicating that HIF1-α could regulate the expression of miR-27-3p, and galectin-3 was a target of miR-27-3p. Finally, overexpression of galectin-3 reduced the protective effect of miR-27-3p on cardiomyocyte injury. The expression levels of HIF1-α were increased, and miR-27-3p was downregulated after AMI. HIF-1α promoted myocardial protection by upregulating miR-27-3p, and downregulation of miR-27-3p promoted myocardium cell injury by targeting galectin-3.

Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform.

In recent decades, with the continuous development of high-throughput sequencing technology, data volume in medical research has increased, at the same time, almost all clinical researchers have their own independent omics data, which provided a better condition for data mining and a deeper understanding of gene functions. However, for these large amounts of data, many common and cutting-edge effective bioinformatics research methods still cannot be widely used. This has encouraged the establishment of many analytical platforms, a portion of databases or platforms were designed to solve the special analysis needs of users, for instance, MG RAST, IMG/M, Qiita, BIGSdb, and TRAPR were developed for specific omics research, and some databases or servers provide solutions for special problems solutions. Metascape was designed to only provide functional annotations of genes as well as function enrichment analysis; BioNumerics and RidomSeqSphere+ perform multilocus sequence typing; CARD provides only antimicrobial resistance annotations. Additionally, some web services are outdated, and inefficient interaction often fails to meet the needs of researchers, such as our previous versions of the platform. Therefore, the demand to complete massive data processing tasks urgently requires a comprehensive bioinformatics analysis platform. Hence, we have developed a website platform, Sangerbox 3.0 (http://vip.sangerbox.com/), a web-based tool platform. On a user-friendly interface that also supports differential analysis, the platform provides interactive customizable analysis tools, including various kinds of correlation analyses, pathway enrichment analysis, weighted correlation network analysis, and other common tools and functions, users only need to upload their own corresponding data into Sangerbox 3.0, select required parameters, submit, and wait for the results after the task has been completed. We have also established a new interactive plotting system that allows users to adjust the parameters in the image; moreover, optimized plotting performance enables users to adjust large-capacity vector maps on the web site. At the same time, we have integrated GEO, TCGA, ICGC, and other databases and processed data in batches, greatly reducing the difficulty to obtain data and improving the efficiency of bioimformatics study for users. Finally, we also provide users with rich sources of bioinformatics analysis courses, offering a platform for researchers to share and exchange knowledge.

1-MNA Ameliorates High Fat Diet-Induced Heart Injury by Upregulating Nrf2 Expression and Inhibiting NF-κB in vivo and in vitro.

High levels of free fatty acids (FFA) are closely associated with obesity and the development of cardiovascular diseases. Recently, nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a potential target for several modern diseases including diabetes. Herein, we explored the underlying mechanisms of NAD metabolism associated with the risk of cardiovascular disease. Our study found that nicotinamide N-methyltransferase (NNMT) mRNA levels were significantly increased in the hearts of FFA-bound-albumin-overloaded mice and in H9C2 cells treated with palmitic acid (PA). We studied the mechanisms underlining the anti-inflammatory and anti-oxidant activities of 1-methylnicotinamide (1-MNA), a metabolite of NNMT. We found a significantly higher level of reactive oxygen species, inflammation, apoptosis, and cell hypertrophy in PA-treated H9C2 cells and this effect was inhibited by 1-MNA treatment. in vivo, 1-MNA improved inflammation, apoptosis, and fibrosis damage in mice and this inhibition was associated with inhibited NF-κB activity. In conclusion, our study revealed that 1-MNA may prevent high fatty diet and PA-induced heart injury by regulating Nrf2 and NF-κB pathways.

Inhibition of Long Noncoding RNA SNHG20 Improves Angiotensin II-Induced Cardiac Fibrosis and Hypertrophy by Regulating the MicroRNA 335/Galectin-3 Axis.

Cardiac fibrosis is a hallmark of various heart diseases and ultimately leads to heart failure. Although long noncoding RNA (lncRNA) SNHG20 has been reported to play important roles in various cancers, its function in cardiac fibrosis remains unclear. The expression of SNHG20 and microRNA 335 (miR-335) in heart tissues of angiotensin II-induced mice and angiotensin II-stimulated mouse cardiomyocyte cell line HL-1 were detected by quantitative real-time PCR (qRT-PCR). Cell viability was evaluated by cell counting kit-8 assay. The expression of galectin-3, fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA), and apoptosis-related proteins [cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)] was detected by Western blotting. Bioinformatics prediction, luciferase reporter assay, and RNA pulldown assay were performed to determine the relationship between SNHG20 and miR-335 as well as miR-335 and Galectin-3. Gain- and loss-function assays were performed to determine the role of SNHG20/miR-335/Galectin-3 in cardiac fibrosis. SNHG20 was significantly upregulated and miR-335 was downregulated in heart tissues of angiotensin II-treated mice and angiotensin II-stimulated HL-1 cells. Downregulation of SNHG20 effectively enhanced cell viability and decreased cell size of HL-1 cells and the expression levels of fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA) and apoptosis-related proteins (cleaved caspase-3 and cleaved PARP), which were induced by angiotensin II treatment. Furthermore, SNHG20 elevated the expression levels of Galectin-3 by directly regulating miR-335. Our study revealed that downregulation of SNHG20 improved angiotensin II-induced cardiac fibrosis by targeting the miR-335/Galectin-3 axis, suggesting that SNHG20 is a therapeutic target for cardiac fibrosis and hypertrophy.

Survival motor neuron protein protects H9c2 cardiomyocytes from hypoxia-induced cell injury by reducing apoptosis.

BACKGROUND: Hypoxia induces cell injury in cardiomyocytes and leads to the development of cardiovascular diseases. The survival motor neuron protein (SMN) is a crucial ubiquitous protein whose functional deficiency causes motor neuron loss seen in spinal muscular atrophy. SMN has shown protective effects on the cardiovascular system and the aim of the present study was to investigate the cardioprotective effects of SMN on hypoxia-induced cell injury. METHODS: Cobalt chloride (CoCl2 ) was used to induce chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was determined by the MTT assay and the mRNA levels of SMN were evaluated by real-time polymerase chain reaction. The protein expression levels of SMN, hypoxia-inducible transcription factor 1α (HIF-1α), and apoptosis-related proteins, such as cytochrome c (Cyt c), B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and cleaved caspase-3 were evaluated by western blot analysis. Cell apoptosis was analysed using annexin V/propidium iodide (PI) staining. RESULTS: Treatment with CoCl2 significantly reduced H9c2 cell viability; the level of HIF-1α, which is a hypoxia-related indicator increased whereas the expression of SMN protein decreased. Hypoxia also induced cardiomyocyte apoptosis, indicated by reduced Bcl-2 expression and elevated cleaved caspase-3, Bax, and cytochrome c levels. Interestingly, SMN, which is a neuron protection factor, ameliorated CoCl2 -induced cell damage by reducing cardiomyocyte apoptosis through upregulation of Bcl-2 and inhibition of cytochrome c, cleaved caspase-3, and Bax expression. CONCLUSION: Survival motor neuron prevents hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, and thereby exerts a protective effect on H9c2 cardiomyocytes.