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Empagliflozin restores cardiac function in obese-diabetic HFpEF mice butfurther alters gene expression

GSE285966 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2026/05/13 Platform GPL28330
At a glance

RNA-seq (gene expression) · mouse · 30 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
30 samples: 8 × WT + Veh + Empa vs 8 × db/db + Aldo vs 7 × db/db + Aldo + Empa vs 7 × WT + VehGroups 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.
Summary (written by the submitters)
Effective treatments for heart failure with preserved ejection fraction (HFpEF) are limited. Empagliflozin, a sodium-glucosecotransporter-2 (SGLT2) inhibitor, provides cardiovascular benefits for patients with HFpEF. SGLT2 expression is virtually absent in cardiomyocytes, hence the exact protective mechanism of empagliflozin is unclear.
Read the full summary ↓
We aimed to study the effect of in vivo empagliflozin treatment on excitation–contraction coupling (ECC), electrophysiology, and gene transcription in a translational two-hit HFpEF mouse model that combines the obese-diabetic leptin receptor-deficient db/db mice with chronic aldosterone infusion (db/db + Aldo). We performed morphometry, echocardiography, cardiomyocyte electrophysiology, intracellular Ca imaging, and whole-heart RNA-sequencing in empagliflozin-treated db/db + Aldo and vehicle control mice. In db/db + Aldo mice, empagliflozin (in vivo, 4weeks) reduced the elevated plasma blood glucose (13 ± 5 mmol/L versus 23 ± 8 mmol/L) and BNP levels, prevented pulmonary congestion, and ameliorated diastolic dysfunction. However, empagliflozin did not reduce cardiac hypertrophy and obesity. In healthy control mice, empagliflozin had no functional effect. Chronic in vivo empagliflozin treatment in db/db + Aldo also normalized the changes in cardiomyocyte electrophysiology and Ca handling properties measured in the absence of empagliflozin in the perfusion solution during cell experiments, indicating a true phenotypic rescue. Differentially expressed gene clusters were identified characteristic of the db/db genotype, aldosterone, and empagliflozin treatments. Interestingly, empagliflozin did not just reverse the HFpEF-altered gene expression but shifted it further away from control to a new expression profile. We conclude that chronic in vivo empagliflozin treatment restores cardiomyocyte electrophysiological and ECC properties, ameliorates diastolic function in cardiometabolic HFpEF, and induces complex gene expression changes.
This dataset
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.

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 GSE285966_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1207072 and SRA study SRP555577. Searching any of these in the dataset finder brings you back here.

Study design
8 × WT + Veh + Empa vs 8 × db/db + Aldo vs 7 × db/db + Aldo + Empa vs 7 × WT + Veh

Supports a between-group comparison across 30 samples.

How we read this: 4 replicated groups read from 30 sample titles; they account for 30 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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