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Age-Related Decline in NCKX4-Mediated Calcium Clearance Accelerates Aortic Remodeling and Drives Early Vascular Aging

GSE316510 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2026/01/21 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 20 samples, each with a distinct title — no replicated groupsGroups 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
Age-related decline in NCKX4-mediated calcium clearance accelerates aortic remodelling and drives early vascular ageingThe Journal of physiology · 2026
Summary (written by the submitters)
Aging is the primary nonmodifiable risk factor for cardiovascular diseases (CVDs), with older women facing a greater risk of CVDs than age-matched men. Vascular smooth muscle cells (VSMCs) dysfunction and impaired calcium (Ca2+) handling are recognized as central contributors to arterial stiffening and calcification. However, the molecular and functional determinants of Ca2+ clearance that drive vascular aging remain poorly understood.
Read the full summary ↓
We identify the (Na+)-sodium/Ca2+-calcium (K+)-potassium-dependent exchanger 4 (NCKX4) as a crucial functional regulator of VSMCs Ca2+ clearance and vascular integrity. NCKX4 (encoded by Slc24A4) expression was significantly reduced in aortas from aged (72-78 weeks) mice, with a pronounced decline in females. Aged-related loss of NCKX4 impaired Ca2+ clearance function and increased calcium-phosphate mineralization. Young (12-15 weeks) Nckx4⁻/⁻ mice revealed fragmentation of elastic fibers, collagen accumulation, wall thickening, and extracellular matrix (ECM) remodeling, all hallmarks of vascular aging that closely resembled those of aged wild-type mice. Transcriptomic profiling showed that loss of NCKX4 alters pathways linked to Ca2+-integrin signaling, ECM turnover and mineralization, including dysregulation of anchorage integrins, microfibril-stabilizing, osteogenic drivers and pro-fibrotic integrins. These findings reveals that an impaired Ca2+ clearance promotes maladaptive inside-out integrin signaling, disrupting VSMCs anchorage, ECM homeostasis and mineralization. Our results establish NCKX4 as a previously unrecognized determinant of vascular aging, whose decline accelerates premature arterial remodeling and calcification. This study therefore, positions NCKX4 as a potential mechanistic link between age, sex-dependent vulnerability, and vascular stiffening, with implications for novel therapeutic strategies targeting Ca2+ handling in CVDs prevention.
Published in
Age-related decline in NCKX4-mediated calcium clearance accelerates aortic remodelling and drives early vascular ageing
Bomfim GHS, Asam K, Patel N et al. · The Journal of physiology 2026 · PMID 41721478 · doi:10.1113/JP290475
This dataset
Open GSE316510 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 GSE316510_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 PRJNA1403026 and SRA study SRP662268. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41721478) ↗
Study design
20 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 10 samples read as cases, 10 as controls.

How we read this: Read from 20 sample titles: 20 distinct titles with little repetition. 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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