Molecular Signatures of HFpEF: Systems Biology in a Cardiac-Centric Large Animal Model
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ABSTRACT:
PROVIDER: PRJNA759257 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15999300.fastq.gz | Fastqsanger.gz | |||
| SRR15999400.fastq.gz | Fastqsanger.gz | |||
| SRR15999301.fastq.gz | Fastqsanger.gz | |||
| SRR15999401.fastq.gz | Fastqsanger.gz | |||
| SRR15999302.fastq.gz | Fastqsanger.gz |
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Project description:In this study the authors used systems biology to define progressive changes in metabolism and transcription in a large animal model of heart failure with preserved ejection fraction (HFpEF). Transcriptomic analysis of cardiac tissue, 1 month post-banding, revealed loss of electron transport chain components, and this was supported by changes in metabolism and mitochondrial function, altogether signifying alterations in oxidative metabolism. Established HFpEF, 4 months post-banding, resulted in changes in intermediary metabolism with normalized mitochondrial function. Mitochondrial dysfunction and energetic deficiencies were noted in skeletal muscle at early and late phases of disease, suggesting cardiac-derived signaling contributes to peripheral tissue maladaptation in HFpEF. Collectively, these results provide insights into the cellular biology underlying HFpEF progression.
2021-09-01 | GSE181184 | GEO
Project description:In this study the authors used systems biology to define progressive changes in metabolism and transcription in a large animal model of heart failure with preserved ejection fraction (HFpEF). Transcriptomic analysis of cardiac tissue, 1-month post-banding, revealed loss of electron transport chain components, and this was supported by changes in metabolism and mitochondrial function, altogether signifying alterations in oxidative metabolism. Established HFpEF, 4 months post-banding, resulted in changes in intermediary metabolism with normalized mitochondrial function. Mitochondrial dysfunction and energetic deficiencies were noted in skeletal muscle at early and late phases of disease, suggesting cardiac-derived signaling contributes to peripheral tissue maladaptation in HFpEF. Collectively, these results provide insights into the cellular biology underlying HFpEF progression.
| S-EPMC8385567 | biostudies-literature
Project description:HFpEF accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. Here, we used a systems biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. The integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.
2025-08-21 | GSE301671 | GEO
Project description:Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF
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Project description:Systems biology of prostate cancer
| PRJEB34826 | ENA
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.
2024-03-05 | PXD045677 | Pride
Project description:Background: HFpEF is a heterogeneous clinical picture that is closely related to extracardiac comorbidities such as obesity, hypertension and diabetes and is associated with chronic, low-grade systemic inflammation. Previous studies on myocardial biopsies of HFpEF patients showed intramyocardial inflammatory activity, suggesting that the inflammatory processes in HFpEF are predominantly systemic and exhibit compartment specific-patterns. Methods: We performed single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) of HFpEF patients (n=6), HFrEF patients (n=8) and healthy controls (n=7) taking obesity status into account. For validation, bulk RNA sequencing was performed on whole blood samples. In parallel, the systemic immune cell response was investigated in a HFpEF mouse model (induced by a high-fat diet plus L-NAME), with one group additionally administered the anti-inflammatory agent nitro-oleic acid (NO₂-OA). Results: Analysis of human PBMCs revealed a HFpEF-specific inflammatory fingerprint, which manifested in obesity-related increased expression of cytokine signaling genes (e.g. CCL2, TNF) and obesity-independent increases in mitochondrial-associated activity. In the mouse model, HFpEF animals showed a comparable increase in inflammatory markers, with treatment with NO₂-OA leading to a partial normalization of immunological signatures and a significant improvement in diastolic function. Conclusion: Our results demonstrate that the immune cells of patients with HFpEF are characterized by a distinct transcriptional immune signature that differs from that of patients with HFrEF. The conserved immunological signatures between humans and mice, and the beneficial effect of NO₂-OA in a preclinical model, provide important translational insights and generate hypotheses for personalized interventions in HFpEF.
2025-07-28 | GSE298172 | GEO
Project description:Background: HFpEF is a heterogeneous clinical picture that is closely related to extracardiac comorbidities such as obesity, hypertension and diabetes and is associated with chronic, low-grade systemic inflammation. Previous studies on myocardial biopsies of HFpEF patients showed intramyocardial inflammatory activity, suggesting that the inflammatory processes in HFpEF are predominantly systemic and exhibit compartment specific-patterns. Methods: We performed single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) of HFpEF patients (n=6), HFrEF patients (n=8) and healthy controls (n=7) taking obesity status into account. For validation, bulk RNA sequencing was performed on whole blood samples. In parallel, the systemic immune cell response was investigated in a HFpEF mouse model (induced by a high-fat diet plus L-NAME), with one group additionally administered the anti-inflammatory agent nitro-oleic acid (NO₂-OA). Results: Analysis of human PBMCs revealed a HFpEF-specific inflammatory fingerprint, which manifested in obesity-related increased expression of cytokine signaling genes (e.g. CCL2, TNF) and obesity-independent increases in mitochondrial-associated activity. In the mouse model, HFpEF animals showed a comparable increase in inflammatory markers, with treatment with NO₂-OA leading to a partial normalization of immunological signatures and a significant improvement in diastolic function. Conclusion: Our results demonstrate that the immune cells of patients with HFpEF are characterized by a distinct transcriptional immune signature that differs from that of patients with HFrEF. The conserved immunological signatures between humans and mice, and the beneficial effect of NO₂-OA in a preclinical model, provide important translational insights and generate hypotheses for personalized interventions in HFpEF.
2025-07-28 | GSE298171 | GEO
Project description:Background: HFpEF is a heterogeneous clinical picture that is closely related to extracardiac comorbidities such as obesity, hypertension and diabetes and is associated with chronic, low-grade systemic inflammation. Previous studies on myocardial biopsies of HFpEF patients showed intramyocardial inflammatory activity, suggesting that the inflammatory processes in HFpEF are predominantly systemic and exhibit compartment specific-patterns. Methods: We performed single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) of HFpEF patients (n=6), HFrEF patients (n=8) and healthy controls (n=7) taking obesity status into account. For validation, bulk RNA sequencing was performed on whole blood samples. In parallel, the systemic immune cell response was investigated in a HFpEF mouse model (induced by a high-fat diet plus L-NAME), with one group additionally administered the anti-inflammatory agent nitro-oleic acid (NO₂-OA). Results: Analysis of human PBMCs revealed a HFpEF-specific inflammatory fingerprint, which manifested in obesity-related increased expression of cytokine signaling genes (e.g. CCL2, TNF) and obesity-independent increases in mitochondrial-associated activity. In the mouse model, HFpEF animals showed a comparable increase in inflammatory markers, with treatment with NO₂-OA leading to a partial normalization of immunological signatures and a significant improvement in diastolic function. Conclusion: Our results demonstrate that the immune cells of patients with HFpEF are characterized by a distinct transcriptional immune signature that differs from that of patients with HFrEF. The conserved immunological signatures between humans and mice, and the beneficial effect of NO₂-OA in a preclinical model, provide important translational insights and generate hypotheses for personalized interventions in HFpEF.
2025-07-28 | GSE298173 | GEO
Project description:DEG and microRNA signatures from HFpEF ventricular biopsies.
| PRJEB62450 | ENA