DNA Methylation Reprograms Metabolic Gene Expression in End-Stage Human Heart Failure
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123976 | GEO | 2019/07/25
REPOSITORIES: GEO
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Project description:RELEVANCE: Identifying early plasma protein biomarkers that predict the development of heart failure (HF) following myocardial infarction (MI) will help to stratify at risk subjects and provide insight into more effective therapeutic strategies. OBJECTIVE/HYPOTHESIS: The goal of this study was to determine markers of HF in African Americans, using plasma samples collected before the development of symptoms. We propose that early plasma glycoprotein changes will link to later development of heart failure. ApolipoproteinF will be the strongest indicator. METHODS: Plasma samples from a subset of Jackson Heart Study participants with a history of MI but without prevalent heart failure (HF) at visit 2 (2005-2008) were analyzed by glycoproteomics. Individuals were grouped into those who experienced subsequent HF hospitalization after visit 2 (n=15; 3 men/ 12 women) and those without HF hospitalization through 2012 (n=45; 24 men/ 21 women). N-linked plasma glycopeptides were quantified by solid-phase extraction coupled to mass spectrometry and identified using RefSeq and SwissProt. Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis (IPA) and linked to clinical characteristics.
2018-08-30 | PXD009870 | Pride
Project description:Background: a considerable numeer of patients with heart failure (HF) present systemic iron deficiency (ID), which is related with worse prognosis and a significant decline in quality of life. The mechanisms that underlay the crosstatlk between myocardial performance, neurohormonal activation and heart metabolism are still to be uncovered. Nonetheless, previous experimental studies have already revealed the potential links between iron, mitochondrial metabolism and heart function. Objectives: The present research attempts to investigate the mechanisms that link HF and ID and to identify potential biomarkers of disease prognosis by determning the gene expression pattern through mRNA transcriptome and PCR analyses. Results: The transcriptome of a first cohort of HF patients was analysed according to the presence of ID, underscoring 1128 overexpressed transcripts in patients with iron dysregulation, which permitted to identify 22 genes involved in biological pathways that could be related to HF and the cellular iron regulation and metabolism. From these 22 selected genes, 6 were found differentially expressed by PCR in a new wider cohort of patients, and comprehensive statistical studies identifying specific genetic patterns in three genes that correlate with prognostic outcomes. Briefly, a genetic expression pattern of the smal integral membrane protein 20 and the sirtuin 7 towards decreased expression (higher Δct) was significantly associated with an increased risk of death and the combined end-point of death and HF hospitalization and the composite. Similarly, the intermediate Δct gene expression pattern of mitochondrial ferritin was also associated of both of previous determined outcomes. Conclusions: Patients with HF present different standards of gene expression according to systemic iron status that involve paramount myocardial metabolic pathways implicated in myocardial function and correlate with prognosis. The study highlights the importance of iron regulation in the comprehensive approach to the treatment of myocardial disease.
2021-11-17 | GSE175739 | GEO
Project description:3 ventricles from E18.5 male mice were pooled for each array. Three arrays per genotype. Title: ERRγ Directs and Maintains the Transition to Oxidative Metabolism in the Post-Natal Heart; Abstract: At birth the heart undergoes a critical metabolic switch to transition from a predominant dependence on carbohydrates during fetal life to a greater dependence on postnatal oxidative metabolism. This remains the principle metabolic state throughout life; although pathologic conditions such as heart failure and cardiac hypertrophy reactivate components of the fetal genetic program to increase carbohydrate utilization. Disruption of the ERRγ gene, which is expressed at high levels in the fetal and postnatal mouse heart, blocks this switch resulting in lactatemia, electrocardiographic (ECG) abnormalities and death during the first week of life. Genomic ChIP-on-chip and expression analysis at E18.5 clearly identifies ERRγ as both a direct and indirect regulator of a nuclear-encoded mitochondrial genetic network that coordinates the postnatal metabolic transition. These findings reveal an unexpected and essential molecular genetic component of the oxidative metabolic gene program in the heart and highlight ERRγ in the study of cardiac hypertrophy and failure. Experiment Overall Design: Fetal mice were collected by caesarean secation. Hearts were stored in RNALater (Qiagen)
2009-04-30 | E-GEOD-8199 | biostudies-arrayexpress
Project description:Adult mammalian cardiomyocytes (CM) are differentiated post-mitotic cells that lack significant proliferative potential through their inability to reactivate the cell cycle postnatally. In the week after birth, the mammalian heart goes through distinct stages of cell cycle progression and differentiation that govern the development of the mature adult CM phenotype. By establishing the fundamental framework of the molecular signals governing these early events after birth, a potential treatment strategy that restores the heart’s ability to proliferate, and in theory, undergo ‘repair’ after injury could be developed. At 0 days (d), 1d, 3d, 5d, 7d, 10d, and 15d after birth, hearts from C57BL/6J wild-type mice were excised and processed for total RNA isolation. Samples were analyzed by genome-wide messenger RNA (mRNA) microarray profiling. All experiments were performed on age- and sex-matched mice, with equal ratio of male to female mice.
2019-10-01 | E-MTAB-8168 | biostudies-arrayexpress
Project description:Abnormalities in metabolism of energetic substrates may play a role in progression of chronic heart failure (HF). The goal of the study was to examine the extent and mechanisms of metabolic alterations in rat model of chronic HF due to volume overload. Volume overload was induced in 3 months old male Wistar rats by aorto-caval fistula. In the phase of symptomatic HF (after 21 weeks), we performed myocardial gene expression analysis. Cardiac tissue gene expression analysis showed downregulation of enzymes of respiratory cycle, mitochondrial fatty acid (FA) oxidation and attenuated expression of proteins responsible for FA translocation/transport (CD36/FAT, FABP3, FATP-1). Simultaneously, we performed gene expression analysis of fat tissue.
2011-10-05 | E-MTAB-190 | biostudies-arrayexpress
Project description:Background: Heart failure (HF) has been recognized as global pandemic with a high rate of associated hospitalization, morbidity and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. Methods: We collected left ventricular heart tissue from 21 HF patients and 9 healthy donors as study cohort and generated multi-level transcriptomic data. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma level in validation cohort (87 HF patients) for predicting HF progression. Results: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in study cohort. The follow-up functional annotations and regulatory network reveal their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its up-regulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content >281.7 ng/ml in plasma was found to be associated with poor survival within one year of heart transplantation from heart failure [Hazard Ratio (HR): 27.52, 95% Confidence Interval (CI): 7.474 to 101.3, Log-rank p-value<1.0×10-4]. Conclusions: Our results suggested that COL1A1 is a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.
2020-01-08 | GSE135055 | GEO
Project description:Myocardial ischemia (MI) is the most common cause of heart failure (HF) in the United States. G protein‑coupled receptor (GPCR) kinase 5 (GRK5) has been found to be upregulated in failing human myocardium. While the canonical role of GRKs is to desensitize receptors via phosphorylation, GRK5 can also translocate to the nucleus of cardiomyocytes where it exerts GPCR‑independent effects that promote maladaptive cardiac hypertrophy. The role of GRK5 in ischemic heart disease is still unknown
2020-06-13 | GSE132701 | GEO
Project description:We characterized the metabolic and cardiac mitochondrial function in a mouse model of non-ischemic HF. Inhibition of nitric oxide synthesis and hypertension, which often present together, are two important risk factors in human non-ischemic HF. Compared with L-NAME L-NG-Nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis or Angiotensin II (AngII), a hypertensive agent treatment alone, L-NAME+AngII induced the most severe HF phenotype characterized by edema, hypertrophy, fibrosis, increased blood pressure and reduced ejection fractions. L-NAME+AngII treated mice had robust deterioration of cardiac mitochondrial function we observed. Microarray analyses revealed majority of the gene changes attributed to the combination of L-NAME+AngII. Pathway analyses indicated significant changes in metabolic pathways such as mitochondrial oxidative phosphorylation, fatty acid metabolism and tricarboxylic acid pathways etc.in L-NAME+AngII hearts. We conclude that combination of L-NAME+AngII exacerbates cardiac contractile and mitochondrial functional de-regulation compared with L-NAME and AngII alone, resulting in non-ischemic HF. This model of heart failure may be highly valuable in studying mechanisms and treatments for non-ischemic heart failure. Twelve week-old C57BL6 male mice were randomly assigned to 4 groups: 1. Control, 2. L-NAME treatment, 3. AngII treatment, 4. L-NAME+AngII treatment.L-NAME (0.3 mg/ml with 1% NaCl) was administered in drinking water. AngII (0.7 mg/kg/day) was administered via subcutaneous micro-osmotic pumps. L-NAME and AngII were administered to mice for 5 weeks and 4 weeks in combination to induce HF or alone to study the effects of the individual agents.
2016-01-19 | E-GEOD-72132 | biostudies-arrayexpress
Project description:We characterized the metabolic and cardiac mitochondrial function in a mouse model of non-ischemic HF. Inhibition of nitric oxide synthesis and hypertension, which often present together, are two important risk factors in human non-ischemic HF. Compared with L-NAME L-NG-Nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis or Angiotensin II (AngII), a hypertensive agent treatment alone, L-NAME+AngII induced the most severe HF phenotype characterized by edema, hypertrophy, fibrosis, increased blood pressure and reduced ejection fractions. L-NAME+AngII treated mice had robust deterioration of cardiac mitochondrial function we observed. Microarray analyses revealed majority of the gene changes attributed to the combination of L-NAME+AngII. Pathway analyses indicated significant changes in metabolic pathways such as mitochondrial oxidative phosphorylation, fatty acid metabolism and tricarboxylic acid pathways etc.in L-NAME+AngII hearts. We conclude that combination of L-NAME+AngII exacerbates cardiac contractile and mitochondrial functional de-regulation compared with L-NAME and AngII alone, resulting in non-ischemic HF. This model of heart failure may be highly valuable in studying mechanisms and treatments for non-ischemic heart failure.
2016-01-19 | GSE72132 | GEO
Project description:High incidence of heart failure (HF) is a typical characteristic of chronic kidney disease (CKD). However, the pathogenesis of CKD-associated HF remains elusive. Here, we investigated the changes in myocardial energy metabolism in CKD mice and explored the underlying mechanisms. To examine genome wide transcriptional changes in the heart of CKD mice, we performed microarray analysis using the Affymetrix Clariom S mouse.
2019-03-16 | GSE126824 | GEO