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Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor

GSE318212 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2026/03/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 4 × Control vs 4 × AngII vs 4 × AngII+LY vs 2 × LYGroups 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
Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptorFrontiers in cardiovascular medicine · 2026
Summary (written by the submitters)
Background: Aortic Stenosis (AS) is a highly prevalent disease involving physiological and structural remodeling of aortic valve, yet lacks effective medical therapy to halt its progression. Serotonin (5HT) signaling has been implicated in valvular disease. We hypothesized that AS is associated with impaired 5HT clearance due to reduced serotonin receptor (SERT) expression and increased 5HT receptor (HTR) activity.
Read the full summary ↓
Methods: Sixty-six patients with severe AS undergoing aortic valve (AV) replacement were enrolled in the study, and samples from their explanted AV were harvested. Anatomically normal control AVs were obtained from transplant donors. Explanted AVs were collected for gene expression analysis and 5-HTTLPR genotyping. Gene expression was assessed by RT2-profiler gene array. In vivo, 8-week-old mice received 28-day Angiotensin-II (AngII) infusions ± HTR2B antagonist (LY272015) through subcutaneous Alzet osmotic-pump implants. AV structure and function were assessed via echocardiography, histology, and RNA sequencing. Human aortic valve interstitial cells (AVICs) were treated with either H2O2 or AngII ± SERT siRNAs to assess 5HT signaling and fibrotic/osteogenic markers. Results: AS patients exhibited reduced SERT and increased HTR expression. Oxidative stress in cultured human AVICs suppressed SERT and induced HTR2B expression. AngII ± SERT siRNA promoted VIC osteogenic marker expression. In mice, AngII caused AV thickening, increased velocities and gradients, and activation of fibrosis and calcification-related gene sets, including serotonin, TGFβ, Wnt/β-catenin, PI3K/Akt, and Notch pathways. Pharmacological inhibition of HTR2B preserved AV structure, normalized transvalvular velocities and pressure gradients, and reversed AngII-induced transcriptional changes. Conclusions: In human and mouse AVs, reduced SERT and elevated HTR2B signaling contribute to early-onset fibro-calcific remodeling. HTR2B inhibition by LY272015 reverses these effects, suggesting it as a potential therapeutic strategy for AS.
Published in
Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor
Levine D, Camillo C, Castillero E et al. · Frontiers in cardiovascular medicine 2026 · PMID 41768577 · doi:10.3389/fcvm.2026.1729078
This dataset
Open GSE318212 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 GSE318212_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 PRJNA1416926 and SRA study SRP672112. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41768577) ↗
Study design
4 × Control vs 4 × AngII vs 4 × AngII+LY vs 2 × LY

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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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