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Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension

GSE269053 Mus musculus (mouse) RNA-seq (gene expression) 21 samples Submitted 2025/01/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 21 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
21 samples: 6 × Heart, chow, Renin, vs 6 × Heart, HFD, novirus, vs 5 × Heart, HFD, Renin, vs 4 × Heart, chow, novirus,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertensionScientific reports · 2025
Summary (written by the submitters)
Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust pre-clinical mouse models of human HFpEF. We have developed a novel “2-hit” mouse model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF.
Read the full summary ↓
C57Bl6/NJ mice fed a high fat diet for at least 10 weeks were administered an AAV8-driven vector resulting in constitutive overexpression of mouse Renin1d. Control mice, HFD only, Renin only and HFD-Renin (aka “HFpEF”) littermates underwent a battery of cardiac and extracardiac phenotyping. HFD-Renin mice demonstrated obesity and insulin resistance, a 2-3-fold increase in circulating renin levels and resulted in 30-40% increase in LVH hypertrophy, preserved systolic function, and diastolic dysfunction indicated by altered E/e’, IVRT, and strain measurements; increased left atrial mass; elevated natriuretic peptides; and exercise intolerance. The transcriptomic and metabolomic signature of HFpEF indicates upregulation of fibrotic pathways and downregulation of metabolic pathways, in particular branched chain amino acid catabolism, similar to human HFpEF data. Treatment of these mice with the sodium-glucose cotransporter 2 inhibitor empagliflozin, a powerful but incompletely understood HFpEF therapy, showed improvement in exercise tolerance, left heart enlargement, and insulin homeostasis. The HFD-Renin mouse model recapitulates many critical features of human HFpEF and allows for dissection of how individual pathogenic drivers contribute to cardiac and peripheral metabolic changes. Multiple HFpEF models will also allow for orthogonal studies and increase validity in pre-clinical research efforts.
Published in
Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension
Berger JH, Shi Y, Matsuura TR et al. · Scientific reports 2025 · PMID 39747575 · doi:10.1038/s41598-024-84515-9
This dataset
Open GSE269053 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269053_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1120029 and SRA study SRP511733. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39747575) ↗
Study design
6 × Heart, chow, Renin, vs 6 × Heart, HFD, novirus, vs 5 × Heart, HFD, Renin, vs 4 × Heart, chow, novirus,

Supports a between-group comparison across 21 samples.

How we read this: 4 replicated groups read from 21 sample titles; they account for 21 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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