Sex modulates genome regulatory system in heart failure in humans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA877032 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21423854_1.fastq.gz | Fastqsanger.gz | |||
| SRR21423854_2.fastq.gz | Fastqsanger.gz | |||
| SRR21423855_1.fastq.gz | Fastqsanger.gz | |||
| SRR21423855_2.fastq.gz | Fastqsanger.gz | |||
| SRR21423856_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 40 |
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Project description:Heart failure and other cardiomyopathies have distinct presentations in males versus females that are often overlooked, leading to ineffective treatment, and contributing to the growing mortality from heart diseases. Understanding the differences in the pathogenesis of heart disease in males and females can guide early diagnostics and sex-specific therapy. Thus, there is a pressing need to investigate the sex-specificity of promoter and enhancer activity in the pathogenesis of heart failure. Here, using cap analysis of gene expression we characterize the sex-specific activity of transcriptional regulatory elements in 17 male and 14 female healthy and failing hearts. We show that differentially expressed transcribed regulatory elements between two sexes are spread throughout the entire genome in healthy and failing atria and ventricles, and are related to immune system, metabolic, cardiomyocyte function, and developmental pathways. Moreover, we found 720 genes with sex-dependent promoter switching of which 40 switched dominant promoters. Among those was CREM, a transcription factor, with a short repressive dominant isoform exclusive for males. CREM is related to extensive β-adrenergic receptor stimulation that leads to elevated arrhythmic activity, hypertrophy and heart dysfunction. Furthermore, we identified metabolic pathways being more responsible for female aging and developmental pathways for male aging. We also showed sex-specific aging patterns, such as age-specific promoter usage of 1,100 genes that behaved differently depending on sex, including UCKL1 and HAND2 linked to uridine metabolism and cardiac development, respectively.
2023-04-27 | GSE212695 | GEO
Project description:Transcriptomics analysis of skeletal muscle in humans with heart failure
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Project description:Autonomic neuronal dysfunction is associated with heart failure (HF). Here, we report that targeted vagal nerve stimulation (VNS) using optogenetics attenuates cardiac remodelling and HF induced by pressure overload. Unbiased approaches revealed that VNS decreased the proportion of the Ccrl2+ macrophage subset, which derived from myeloid monocytes and exhibited a distinct tumour necrosis factor-alpha (TNFα)-responsive, pro-hypertrophic, and profibrotic signature. Elimination of Ccrl2+ macrophages prevented cardiac remodelling and HF. Functional characterisation by Ccrl2+ macrophage-specific overexpression or global genetic loss of α7 nicotinic acetylcholine receptor (α7nAChR) highlighted its crucial contribution to VNS-mediated cardioprotection. Mechanistically, activation of α7nAChR inhibited the TNFα responsiveness through upregulated expression of the transcription factor NRF2. Cardiac Ccrl2+ macrophages and TNFα-responsive proteins were positively correlated with cardiac remodelling and dysfunction in humans. Finally, an α7nAChR agonist effectively blocked the development of HF. These results suggest that the vagal neuroimmune axis modulates heart failure and is a promising target for treatment.
2025-05-31 | GSE296034 | GEO
Project description:Autonomic neuronal dysfunction is associated with heart failure (HF). Here, we report that targeted vagal nerve stimulation (VNS) using optogenetics attenuates cardiac remodelling and HF induced by pressure overload. Unbiased approaches revealed that VNS decreased the proportion of the Ccrl2+ macrophage subset, which derived from myeloid monocytes and exhibited a distinct tumour necrosis factor-alpha (TNFα)-responsive, pro-hypertrophic, and profibrotic signature. Elimination of Ccrl2+ macrophages prevented cardiac remodelling and HF. Functional characterisation by Ccrl2+ macrophage-specific overexpression or global genetic loss of α7 nicotinic acetylcholine receptor (α7nAChR) highlighted its crucial contribution to VNS-mediated cardioprotection. Mechanistically, activation of α7nAChR inhibited the TNFα responsiveness through upregulated expression of the transcription factor NRF2. Cardiac Ccrl2+ macrophages and TNFα-responsive proteins were positively correlated with cardiac remodelling and dysfunction in humans. Finally, an α7nAChR agonist effectively blocked the development of HF. These results suggest that the vagal neuroimmune axis modulates heart failure and is a promising target for treatment.
2025-05-03 | GSE295812 | GEO
Project description:Autonomic neuronal dysfunction is associated with heart failure (HF). Here, we report that targeted vagal nerve stimulation (VNS) using optogenetics attenuates cardiac remodelling and HF induced by pressure overload. Unbiased approaches revealed that VNS decreased the proportion of the Ccrl2+ macrophage subset, which derived from myeloid monocytes and exhibited a distinct tumour necrosis factor-alpha (TNFα)-responsive, pro-hypertrophic, and profibrotic signature. Elimination of Ccrl2+ macrophages prevented cardiac remodelling and HF. Functional characterisation by Ccrl2+ macrophage-specific overexpression or global genetic loss of α7 nicotinic acetylcholine receptor (α7nAChR) highlighted its crucial contribution to VNS-mediated cardioprotection. Mechanistically, activation of α7nAChR inhibited the TNFα responsiveness through upregulated expression of the transcription factor NRF2. Cardiac Ccrl2+ macrophages and TNFα-responsive proteins were positively correlated with cardiac remodelling and dysfunction in humans. Finally, an α7nAChR agonist effectively blocked the development of HF. These results suggest that the vagal neuroimmune axis modulates heart failure and is a promising target for treatment.
2025-05-31 | GSE296255 | GEO
Project description:Autonomic neuronal dysfunction is associated with heart failure (HF). Here, we report that targeted vagal nerve stimulation (VNS) using optogenetics attenuates cardiac remodelling and HF induced by pressure overload. Unbiased approaches revealed that VNS decreased the proportion of the Ccrl2+ macrophage subset, which derived from myeloid monocytes and exhibited a distinct tumour necrosis factor-alpha (TNFα)-responsive, pro-hypertrophic, and profibrotic signature. Elimination of Ccrl2+ macrophages prevented cardiac remodelling and HF. Functional characterisation by Ccrl2+ macrophage-specific overexpression or global genetic loss of α7 nicotinic acetylcholine receptor (α7nAChR) highlighted its crucial contribution to VNS-mediated cardioprotection. Mechanistically, activation of α7nAChR inhibited the TNFα responsiveness through upregulated expression of the transcription factor NRF2. Cardiac Ccrl2+ macrophages and TNFα-responsive proteins were positively correlated with cardiac remodelling and dysfunction in humans. Finally, an α7nAChR agonist effectively blocked the development of HF. These results suggest that the vagal neuroimmune axis modulates heart failure and is a promising target for treatment.
2025-05-03 | GSE295813 | GEO
Project description:Heart failure is a multisystem syndrome caused by structural and functional defects in multiple tissues. The study aims to identify differentially regulated genes in skeletal muscle of heart failure patients. Here, we obtained biopsies from the pectoralis major muscle and performed RNA sequencing to profile the gene expression patterns from six heart failure patients and three healthy controls.
2020-09-07 | E-MTAB-8531 | biostudies-arrayexpress
Project description:Sex modulates microglia in the aging brain
| PRJNA758568 | ENA
Project description:We developed a cellular model to study sex differences in humans. Using somatic cells from a mosaic Kleinefelter patient, we generated isogenic human induced pluripotent stem cell lines with different sex chromosome complements – 47,XXY / 46,XX / 46,XY and 45,X0.
2022-11-24 | GSE145079 | GEO
Project description:LCMS files from tryptic digests of ~1-4 mg piece of heart ventricular tissue from human with ischemic heart failure and non-failing controls.
Specimen number correspond to .raw files as follows:
Ischemic Heart failure -
54687.1; HF_1_phos.raw
53148.1; HF_2_phos.raw
53589.2; HF_3_phos.raw
54146.1; HF_4_phos.raw
52935.1; HF_5_phos.raw
Non-failing -
52941.1; NHF_1_phos.raw
52777.1; NHF_2_phos.raw
53019.2; NHF_3_phos.raw
53058.1; NHF_4_phos.raw
52621.1; NHF_5_phos.raw
2022-12-07 | MSV000090858 | MassIVE