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FOXO1 integrates endothelial hemodynamic, inflammatory and metabolic pathways in atherosclerosis [LSS]

GSE313932 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/02/24 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
Homo sapiens (human)
Samples
12 samples: 3 × siCtrl_Static vs 3 × siCtrl_LSS vs 3 × siFOXO1_Static vs 3 × siFOXO1_LSSGroups 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
FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in AtherosclerosisCirculation research · 2026
Summary (written by the submitters)
Atherosclerosis occurs preferentially in regions of disturbed or low fluid shear stress (FSS), whereas physiological laminar FSS protects against disease by suppressing endothelial inflammation. Pro- vs anti-inflammatory programs are associated with glycolysis vs mitochondrial metabolism, respectively. Endothelial cells (ECs) sensing FSS from blood flow regulate these responses, but the underlying mechanisms are poorly understood.
Read the full summary ↓
The transcription factor Forkhead box protein O1 (FOXO1) is known to regulate endothelial metabolism, yet its role in FSS-regulated endothelial inflammation remains largely unclear. We found that Oscillatory FSS and inflammatory cytokines induce, whereas physiological FSS inhibits FOXO1 nuclear translocation. RNA sequencing revealed that FOXO1 depletion in ECs upregulates the protective flow-responsive transcription factors KLF2/4 and reduces oscillatory FSS-induced inflammatory genes. Inhibition of FOXO1 nuclear translocation by physiological FSS is mediated via a KLF2-CDK2 pathway, with the latter phosphorylating FOXO1 at S249. Artery ECs-specific deletion of FOXO1 significantly reduces atherosclerotic plaque formation in hyperlipidemic mice. Inhibition of glycolysis attenuates OSS-induced FOXO1 nuclear translocation, suggesting a role for metabolic regulation. Notably, treatment with lactate promotes FOXO1 nuclear localization and lactylation, which is mediated by a lactyltransferase AARS1 (Alanyl-tRNA synthetase). These findings identify FOXO1 as a key mediator linking atheroprone flow and endothelial inflammation, suggesting potential new therapeutic targets for treating atherosclerotic cardiovascular disease.
Published in
FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis
Deng H, Zhang X, Wang Y et al. · Circulation research 2026 · PMID 41738126 · doi:10.1161/CIRCRESAHA.125.327592
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 GSE313932_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 PRJNA1387386 and SRA study SRP655596. Searching any of these in the dataset finder brings you back here.

Study design
3 × siCtrl_Static vs 3 × siCtrl_LSS vs 3 × siFOXO1_Static vs 3 × siFOXO1_LSS

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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