Evidence map›Paper›PMID 40924347›Full record

ArticleHigh blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension2025

Targeting the Epigenetic Remodeler GCN5 Prevents Vascular Oxidative Stress and Endothelial Dysfunction in Obesity: Insights in Patients with Cardiometabolic Disease.

Sarah Costantino, Shafeeq Mohammed, Alessandro Mengozzi, Emiliano Duranti, Valentina Delfine, Martin A Geiger, Nazha Hamdani, Stefano Taddei, Stefano Masi, Agostino Virdis and 1 more

Abstract read
In one paragraph

Article in High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Sarah CostantinoCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland. sarah.costantino@uzh.ch.
Shafeeq MohammedCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Alessandro MengozziCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Emiliano DurantiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Valentina DelfineCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Martin A GeigerCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Nazha HamdaniInstitute of Physiology, Ruhr University, Bochum, Germany.
Stefano TaddeiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Stefano MasiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Agostino VirdisDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Francesco PaneniCenter for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich and University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland. francesco.paneni@uzh.ch.ORCID http://orcid.org/0000-0001-6483-7844

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEpigenetic changes are important modulators of gene expression. The histone acetyltransferase gene non-derepressible 5 (Gcn5) is emerging as a pivotal epigenetic player in metabolism and cancer, yet its role in obesity and cardiovascular disease remains elusive.

aimsTo investigate Gcn5 role in obesity-related endothelial dysfunction.

methodsHuman aortic endothelial cells (HAECs) were exposed to vehicle or palmitic acid (200 uM) in the presence or in the absence of the Gcn5 pharmacological inhibitor CPTH2 or gene silencing. Ex-vivo inhibition of Gcn5 was performed in aortic rings from diet-induced obese and control mice. Chromatin immunoprecipitation (ChIP) was performed to investigate the epigenetic regulation of Nox2 promoter. In parallel, Gcn5/Nox2 expression was assessed by real-time PCR in vascular specimens isolated from obese patients and age-matched healthy controls. Endothelial-dependent vasodilation was also assessed in human vessels.

resultsPA increased Gcn5 gene expression in HAECs. Gcn5 upregulation was associated with increased expression of the pro-oxidant enzyme Nox2. Interestingly, either Gcn5 inhibition or gene silencing prevented PA-induced Nox2 upregulation and oxidative stress accumulation. ChiP assay showed increased Gcn5 occupancy and enhanced histone 3 acetylation of lysine 14 (H3K14ac) on Nox2 promoter. In aortic rings from obese mice, pharmacological inhibition of Gcn5 by CPTH2 rescued endothelial-dependent vasorelaxation as compared to vehicle. Finally, Gcn5 was increased in vessels from obese patients and correlated with Nox2 expression and endothelial dysfunction.

conclusionsOur findings shed light on the importance of epigenetic regulation in obesity and pinpoint Gcn5 as a therapeutic target to prevent endothelial dysfunction in cardiometabolic disease.

Indexed as

Endothelial CellsEndothelium, VascularEpigenesis, GeneticObesityOxidative Stressp300-CBP Transcription FactorsVasodilationAcetylationAnimalsCase-Control StudiesCells, CulturedDisease Models, AnimalEnzyme InhibitorsFemaleHumansMaleCYBB protein, humanCybb protein, mouseEnzyme InhibitorsNADPH Oxidase 2p300-CBP-Associated Factorp300-CBP Transcription FactorsPalmitic AcidCardiometabolic diseaseChromatinEndothelial dysfunctionEpigeneticsObesityOxidative stress

Identifiers

PMID40924347
PMCPMC12474637

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.