Dataset Information

Myocardial Injury Caused by Chronic Alcohol Exposure——A Pilot Study Based on Proteomic

ABSTRACT: Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway related to the biosynthesis of unsaturated fatty acids and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study the myocardial damage caused by alcohol, the mouse model of ACM successfully established previously was used to perform proteomics analysis on myocardial specimens. Fifty-six differentially expressed proteins (DEPs) were identified, and they are involved in the KEGG pathway related to fatty acid biosynthesis, lipid metabolism, oxidative stress, and the development of dilated cardiomyopathy (DCM). The present study further demonstrated the underlying causes of myocardial damage caused by chronic alcohol consumption and lays the foundation for further research to clarify the underlying mechanism of ACM.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Xiaonan Ma

LAB HEAD: Zhipeng Cao

PROVIDER: PXD032949 | Pride | 2022-08-12

REPOSITORIES: Pride

ACCESS DATA

Publications

Myocardial Injury Caused by Chronic Alcohol Exposure-A Pilot Study Based on Proteomics.

Ma Xiaonan X Liao Zihan Z Li Rongxuan R Xia Wei W Guo Honghui H Luo Jiawei J Sheng Huaxin H Tian Meihui M Cao Zhipeng Z

Molecules (Basel, Switzerland) 20220703 13

Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by c ...[more]

PMID: 35807529

Similar Datasets

Project description:Alcohol is a major risk factor for hepatocellular carcinoma (HCC) although the mechanisms underlying the alcohol-related liver carcinogenesis are still poorly understood. Alcohol is known to increase hepatocarcinogenesis possibly by inducing aberrant DNA methylation through the reduced provision of methyl groups within the hepatic one-carbon metabolism. Whether the epigenetically-regulated pathways in alcohol-associated HCC can be reversible or modifiable by nutritional factors is unknown. The aim of the present study was to investigate the genome wide promoter DNA methylation profiles along with array-based, gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients the methylation status and transcriptional levels of all annotated genes were compared by analyzing HCC tissue and the cancer-free surrounding liver tissue, following curative surgery. After merging both the DNA methylation and gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced and 56 hypomethylated-repressed genes. A number of potentially novel candidate tumor-suppressor genes (FAM107A, IGFALS, MT1G, MT1H, RNF180) demonstrated promoter hypermethylation and transcriptional repression in alcohol-associated HCC. Notably, promoter DNA methylation appeared as the regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolic pathway (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16) and SHMT1, a key gene within one-carbon metabolism. A genome-wide DNA methylation approach linked up with array-based gene expression profiles allowed identifying a number of novel, epigenetically-regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically-regulated through promoter DNA methylation in alcohol-associated hepatocarcinogenesis. 16 samples (8 control samples from non-neoplastic liver tissue, 8 test samples from hepatocellular carcinoma) from 8 patients affected from hepatocellular carcinoma were analyzed.

Project description:Heart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNAM-bM-^@M-^Starget-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers. Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).

Project description:Background: Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all heart failure but has few effective therapies. Recent human myocardial transcriptomics and metabolomics have revealed major differences between HFpEF, HF with reduced EF (HFrEF), and controls. How this translates at the protein level is currently unknown. Methods: Myocardial tissue from patients with HFpEF and non-failing donor controls was analyzed by data-dependent (DDA, n=10 HFpEF, n=9 controls) and data-independent (DIA, n=44 HFpEF, n=5 controls) mass spectrometry-based proteomics. Previously reported myocardial proteomic data from end-stage HFrEF and controls were also used. Differential protein expression analysis, machine learning and pathway enrichment were integrated with clinical characteristics and myocardial transcriptomics. Results: DDA-MS proteomics identified 88 significantly upregulated and 248 down-regulated proteins in HFpEF vs controls, out of 1996 identified proteins. Principal component analysis of DDA-MS proteomics found HFpEF was separated into 2 sub-groups: one being similar to controls the other quite disparate. Top proteins contributing to the separation of HFpEF subgroups were enriched in actin/myosin binding, regulation of DNA replication/repair, transcription, and translation. Downregulated proteins in HFpEF vs controls were enriched in pathways related to ribosome structure, transmembrane transporters, metabolic enzymes, and oxidative phosphorylation (OxPhos) proteins. Enriched pathways for proteins upregulated in HFpEF related to actin and phospholipid binding, growth factor signaling, kinase regulation, and glycolysis. Ingenuity pathway analysis predicted downregulation of protein translation, mitochondrial function, and glucose and fat metabolism in HFpEF. OxPhos gene (increased) versus protein (decreased) expression was discordant in HFpEF. The second DIA proteomic analysis also yielded two HFpEF sub-groups; the one most different from controls also having reduced OxPhos and protein translation pathways. A higher proportion of these patients also had severe obesity. Conclusions: Integrative proteomics, transcriptomics, and pathway analysis supports a translational defect particularly involving mitochondrial, ribosomal and protein translation proteins in HFpEF. Patients with more distinct proteomic signatures from control were more often very obese. The results support therapeutic efforts targeting metabolism, mitochondrial function, and protein translation in this subgroup.

Dataset Information

Myocardial Injury Caused by Chronic Alcohol Exposure——A Pilot Study Based on Proteomic

Publications

Myocardial Injury Caused by Chronic Alcohol Exposure-A Pilot Study Based on Proteomics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure