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Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome changes in two translational HFpEF murine models: Aetiology and sex-dependent differences

GSE284354 Mus musculus (mouse) RNA-seq (gene expression) 23 samples Submitted 2025/12/02 Platform GPL28330
At a glance

RNA-seq (gene expression) · mouse · 23 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
23 samples: 8 × Treated - DBDB Aldo vs 7 × Control - DBDB Aldo vs 4 × Control - HFD-Lname vs 4 × Treated - HFD-LnameGroups 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
Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: etiology and sex-dependent differencesAmerican journal of physiology. Heart and circulatory physiology · 2026
Summary (written by the submitters)
Heart failure (HF) with preserved ejection fraction (HFpEF) comprises heterogenous clinical phenotypes and presence of various co-morbidities. Recent two-hit translational animal models, including the hypertensive, nitrosative-stressed mice fed with high-fat diet and L-NAME (HFD+L-NAME) and the obese-diabetic leptin receptor-deficient db/db mice with excess aldosterone (db/db+Aldo), may phenocopy select subgroups of HFpEF.
Read the full summary ↓
We systematically compared mechanisms of excitation-contraction coupling (ECC), electrophysiology, and gene transcription in these key preclinical HFpEF models and between sexes to advance translation. We performed morphometry, echocardiography, cellular electrophysiology, intracellular Ca2+ imaging, and RNA-sequencing. The multiorgan HFpEF phenotype showed key differences between the 2 models, db/db+Aldo mice were markedly obese, had severe hyperglycaemia and hepatomegaly, whereas male HFD+L-NAME mice had more pronounced cardiac hypertrophy. Diastolic dysfunction was more severe in db/db+Aldo mice and worse in females therein, whereas female sex was protective in HFD+L-NAME. Marked proarrhythmic action potential (AP) changes (AP prolongation, increased short-term variability and alternans threshold) occurred in db/db+Aldo (in both sexes), these AP changes were less severe in male HFD+L-NAME and absent in female HFD+L-NAME. In line with these, differential ionic current and Ca2+ handling changes occurred between these two HFpEF models and between sexes in each model. RNA-sequencing revealed highly distinctive gene expression profiles between HFpEF models. We conclude that marked differences exist in cardiomyocyte ECC, electrophysiology, and gene expression between HFD+L-NAME and db/db+Aldo mice and between sexes. This indicates that a combination of translational HFpEF models that mimic select HFpEF sub-phenogroups are needed to better understand HFpEF mechanisms for therapeutic drug development.
Published in
Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: etiology and sex-dependent differences
Hegyi B, Bailey LRJ, Mira Hernandez J et al. · American journal of physiology. Heart and circulatory physiology 2026 · PMID 41407304 · doi:10.1152/ajpheart.00227.2025
This dataset
Open GSE284354 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 GSE284354_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 PRJNA1198874 and SRA study SRP551726. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41407304) ↗
Study design
8 × Treated - DBDB Aldo vs 7 × Control - DBDB Aldo vs 4 × Control - HFD-Lname vs 4 × Treated - HFD-Lname

Supports a case/control comparison: 12 samples read as cases, 11 as controls.

How we read this: 4 replicated groups read from 23 sample titles; they account for 23 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
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