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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction

ABSTRACT: Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction

PROVIDER: PRJNA1003518 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25573504_1.fastq.gz	Fastqsanger.gz
	SRR25573504_2.fastq.gz	Fastqsanger.gz
	SRR25573505_1.fastq.gz	Fastqsanger.gz
	SRR25573505_2.fastq.gz	Fastqsanger.gz
	SRR25573406.fastq.gz	Fastqsanger.gz

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [scRNA-seq]

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.

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [6 wks]

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [control vs HF]

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [6 wks]

Project description:Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [6 wks]

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [scRNA-seq]

Project description:Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [scRNA-seq]

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [control vs HF]

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Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction

Project description:This SuperSeries is composed of the SubSeries listed below.

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Molecular and Cellular Mechanisms of Heart Failure With Preserved Ejection Fraction

Project description:To understand the cellular mechanisms of heart failure with preserved ejection fraction (HFpEF), We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction (TAC) in lean C57Bl/6J (HFrEF phenotype) or obese/diabetic B6.Cg-Lepob/J (ob/ob) mice (HFpEF phenotype) followed by single-nuclei RNA-seq (snRNA-seq) and targeted manipulation of a top ranked signaling pathway (glucagon receptor signaling) differentially affected in the two experimental cohorts.

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Myeloid Cell Derived IL1b Contributes to Pulmonary Vascular Remodeling in Heart Failure with Preserved Ejection Fraction

Project description:Goals and objectives of this study were to determine by bulk RNA-sequencing transcriptomic changes that occur in the lungs of a murine model of heart failure with preserved ejection fraction caused by administration of high fat diet and eNOS inhibitor L-NAME.

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