Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA246309 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA-Seq Identifies Novel Myocardial Gene Expression Signatures of Heart Failure [RNA-seq]
| PRJNA246308 | ENA
Project description:RNA-Seq Identifies Novel Myocardial Gene Expression Signatures of Heart Failure
| PRJNA246307 | ENA
Project description:Fibrosis is important pathogenesis in heart failure with preserved ejection fraction (HFpEF). We previously reported that the overexpression of cardiac transcription factors, Mef2c/Gata4/Tbx5/Hand2 (MGTH) could directly reprogram cardiac fibroblasts (CFs) into induced CMs (iCMs) and reduce fibrosis. Here we show that in vivo cardiac reprogramming generated iCMs from resident CFs, improved cardiac function, and reversed fibrosis in HFpEF model using a novel transgenic mouse system. RNA-seq revealed that the MGTH activated the cardiac program and concomitantly suppressed fibroblast and inflammatory signatures. Thus, cardiac reprogramming improves HFpEF via myocardial regeneration and anti-fibrosis.
2024-12-14 | GSE218733 | GEO
Project description:Single cell sequencing in peripheral blood mononuclear cells (PBMCs) revealed a novel human-specific long noncoding RNA called heart-failure associated transcript 4 (HEAT4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction (AMI) and cardiogenic shock (CS). The transcriptional regulation of HEAT4 was verified through cytokine treatment and single cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA–protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB-17-Prkdc scid/Rj mice.
2024-08-14 | PXD052076 | Pride
Project description:Chronic pressure overload initiates a series of molecular alterations in the human heart that predate macroscopic organ-level remodeling and downstream heart failure (HF). We hypothesized that integrating easily accessible circulating mediators (proteome) with their expression in the heart (transcriptome) may prioritize targets for study in human pressure overload. Among individuals with severe aortic stenosis (AS)—a pressure overload state—we measured the circulating proteome (Olink) and examined associations with myocardial structure/function (N=519), cardiac MRI-based tissue fibrosis (N=145), and outcomes in AS (N=802). We constructed proteomic signatures of cardiac remodeling and tested their association with HF in the UK Biobank (N=36,668). For proteo-transcriptional integration, we examined a "remodeling proteome” prioritized by proteome-phenotype relations at the transcriptional level via single nuclear RNA-sequencing (snRNA-seq) in 20 human hearts (11 with AS at the time of surgical aortic valve replacement [AVR] and 9 donor hearts not used for transplantation). We identified three principal components of myocardial remodeling (across 12 echocardiographic measures in 503 patients with AS) loaded on cardiac morphology, systolic, and diastolic function traits. Proteins associated with these components (the “remodeling proteome”) specified both known and novel mediators of fibrosis, hypertrophy, and oxidative stress, several of which were associated with interstitial fibrosis by cardiac MRI. Proteomic signatures of remodeling were strongly linked to mortality (AS cohort and UK Biobank) and incident HF (UK Biobank). At a myocardial level, we observed broad differential expression of genes encoding the remodeling proteome between AS and donor hearts, featuring convergent fibrosis pathways (WNT9A, ITGA6, AGRN, CRIM1, SEMA4C, LAYN, PTX3, HMOX1) and metabolic-inflammatory signaling (ENPP2/ATX, TNF), among others. Differential expression of proteo-transcriptionally prioritized genes was prominent in fibroblasts, cardiomyocytes, and endothelial cells. Proteo-transcriptional prioritization in human pressure overload hearts identifies both known and novel targets that are mechanistically relevant to HF pathogenesis. Future integrative studies to index circulating biomarkers over time to myocardial tissue level is warranted to inform pathways of HF progression.
2025-05-01 | GSE262690 | GEO
Project description:Myocardial fibrosis leads to cardiac dysfunction and arrhythmias in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. Here, RNA sequencing identifies Forkhead Box1 (FoxO1) signaling as abnormal in HFpEF hearts. Genetic suppression of FoxO1 alters the intercellular communication between cardiomyocytes and fibroblasts, alleviates abnormal diastolic relaxation, and reduces arrhythmias. Targeted downregulation of FoxO1 in activated fibroblasts reduces cardiac fibrosis, blunts arrhythmogenesis and improves diastolic function in HFpEF. These results not only implicate FoxO1 in arrhythmogenesis and lusitropy but also demonstrate that pro-fibrotic cardiomyocyte-fibroblast communication can be corrected, constituting a novel therapeutic strategy for HFpEF.
2024-11-17 | GSE240401 | GEO
Project description:Myocardial fibrosis leads to cardiac dysfunction and arrhythmias in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. Here, RNA sequencing identifies Forkhead Box1 (FoxO1) signaling as abnormal in HFpEF hearts. Genetic suppression of FoxO1 alters the intercellular communication between cardiomyocytes and fibroblasts, alleviates abnormal diastolic relaxation, and reduces arrhythmias. Targeted downregulation of FoxO1 in activated fibroblasts reduces cardiac fibrosis, blunts arrhythmogenesis and improves diastolic function in HFpEF. These results not only implicate FoxO1 in arrhythmogenesis and lusitropy but also demonstrate that pro-fibrotic cardiomyocyte-fibroblast communication can be corrected, constituting a novel therapeutic strategy for HFpEF.
2024-11-17 | GSE240400 | GEO
Project description:Myocardial fibrosis leads to cardiac dysfunction and arrhythmias in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. Here, RNA sequencing identifies Forkhead Box1 (FoxO1) signaling as abnormal in HFpEF hearts. Genetic suppression of FoxO1 alters the intercellular communication between cardiomyocytes and fibroblasts, alleviates abnormal diastolic relaxation, and reduces arrhythmias. Targeted downregulation of FoxO1 in activated fibroblasts reduces cardiac fibrosis, blunts arrhythmogenesis and improves diastolic function in HFpEF. These results not only implicate FoxO1 in arrhythmogenesis and lusitropy but also demonstrate that pro-fibrotic cardiomyocyte-fibroblast communication can be corrected, constituting a novel therapeutic strategy for HFpEF.
2024-11-17 | GSE240403 | GEO