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Loss of SIRT5 accelerates the development of pressure-overload induced heart failure upon dysregulating purine and pyrimidine metabolism

GSE280863 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/12/02 Platform GPL13112
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 6 × Whole heart tissue, Control Sham, vs 6 × Whole heart tissue, cSirt5KO Sham, vs 6 × Whole heart tissue, Control TAC, vs 6 × Whole heart tissue, cSirt5KO TAC,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
Cardiomyocyte-Specific Deletion of Sirtuin 5 Accelerates the Development of Heart Failure Upon Dysregulating Purine MetabolismActa physiologica (Oxford, England) · 2025
Summary (written by the submitters)
Objectives: To explore how modulation of cardiomyocyte SIRT5 levels affects the development of pathological cardiac remodeling and dysfunction. Background: SIRT5 is a mitochondrial NAD+-dependent deacylase, which regulates metabolic enzymes upon desuccinylation, demalonylation, and deglutarylation. Its role in the development of heart failure is not completely understood.
Read the full summary ↓
Methods: Mice with cardiomyocyte-specific Sirt5 deletion (Sirt5-/-) or Sirt5 overexpression (cSirt5-Tg) underwent transverse aortic constriction (TAC) or Sham surgery. Cardiac structure and function were assessed by echocardiography and quantification of myocardial fibrosis and cardiomyocyte cell size. Metabolomic analysis and RNA sequencing were performed to identify potential novel pathways regulated by SIRT5. Results: While cardiac structure and function were similar in cSirt5-Tg compared to control mice, cSirt5-/- mice displayed exacerbated cardiac dilation, dysfunction, and fibrosis following TAC. Accumulation of metabolites involved in purine metabolism, particularly inosine and hypoxanthine, and reductions in nucleosides, adenosine and adenine, and nucleotides, AMP and ADP, were observed in hearts of cSirt5-/- mice and following TAC. Moreover, transcriptional analysis revealed upregulation of purine-nucleoside phosphorylase (PNP) and 5' nucleotidase, ecto (NT5E) and downregulation of adenosine kinase (ADK), which is likely to contribute to enhanced degradation of purine nucleotides and resulting accumulation of inosine and hypoxanthine in hearts of cSirt5-/- mice following TAC. Lastly, reduced SIRT5 expression and protein succinylation in left-ventricular tissue of patients with heart failure correlates with reduced ADK expression. Conclusions: Loss of SIRT5 aggravates cardiac remodeling and dysfunction in response to chronic pressure-overload possibly by dysregulation of genes involved in purine and pyrimidine metabolism, resulting in impaired ATP regeneration from adenosine.
Published in
Cardiomyocyte-Specific Deletion of Sirtuin 5 Accelerates the Development of Heart Failure Upon Dysregulating Purine Metabolism
Byrne NJ, Koentges C, Pfeil K et al. · Acta physiologica (Oxford, England) 2025 · PMID 41104836 · doi:10.1111/apha.70120
This dataset
Open GSE280863 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 GSE280863_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 PRJNA1180940 and SRA study SRP542609. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41104836) ↗
Study design
6 × Whole heart tissue, Control Sham, vs 6 × Whole heart tissue, cSirt5KO Sham, vs 6 × Whole heart tissue, Control TAC, vs 6 × Whole heart tissue, cSirt5KO TAC,

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 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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