What question did this study set out to answer?

The study aims to identify the role of Atox1 in cardiac hypertrophy associated with heart failure.

January 10, 2026Scientific Reports0 citationsOpen Access

The effect of cuproptosis-related gene Atox1 on cardiac hypertrophy in heart failure was investigated based on bioinformatics analysis

HZHui ZhouTongji University MYMing YangZhejiang Chinese Medical University HJHongfeng Jin

Key Result

Atox1 was overexpressed 3.47-fold in heart failure-associated cardiac hypertrophy and its knockdown inhibited cuproptosis and cardiomyocyte hypertrophy.

Key Points

The study aims to identify the role of Atox1 in cardiac hypertrophy associated with heart failure.
Utilized WGCNA and differential analysis on a dataset from the GEO database.
Identified and analyzed cuproptosis-related genes in heart failure.
Established a mouse model of cardiac hypertrophy using the transverse aortic constriction method.
Conducted in vitro experiments treating H9c2 cardiomyocytes with Ang II and Atox1 knockdown.
Identified Atox1 as a highly expressed gene in heart failure-related samples.
Demonstrated that Atox1 knockdown inhibited cuproptosis and reduced cardiomyocyte hypertrophy.
Observed significant overexpression of Atox1 in the mouse model (fold change = 3.47).
Increased levels of SLC31A1 and FDX1 proteins indicated active cuproptosis.

Structured PICO

Does Atox1 knockdown prevent cardiac hypertrophy and cuproptosis in heart failure models?

Population

Bioinformatics datasets (GSE101977, GSE66630, GSE122930), 8-week-old male C57BL/6 mice subjected to transverse aortic constriction (TAC), and rat cardiomyocytes (H9c2) treated with Ang II to simulate cardiac hypertrophy.

Intervention

Atox1 knockdown (si-Atox1) in vitro

Comparator

Sham surgery (in vivo) and negative control siRNA (si-NC) (in vitro)

Outcome

Cardiac hypertrophy (echocardiographic parameters, cell surface area, ANP, BNP, β-MHC) and cuproptosis markers (SLC31A1, FDX1, Dlat aggregation, intracellular Cu+)surrogate

Atox1 promotes cardiomyocyte hypertrophy by regulating intracellular copper homeostasis and cuproptosis, suggesting it as a potential therapeutic target for heart failure.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Heart failure (HF) represents the final stage of multiple cardiovascular diseases. Cuproptosis may play an important role in the progression of HF. This study aimed to identify cuproptosis-related biomarkers in HF and elucidate their potential regulatory mechanisms. We downloaded the HF-related bulk dataset from the GEO database for performing WGCNA and differential analysis. A total of 5,563 HF-related co-expressed genes were identified. By intersecting the above genes with cuproptosis-associated genes, we identified three candidates (DBT, Atox1 and DLD) that are potentially involved in cardiac hypertrophy in HF. Among them, DBT and DLD were lowly expressed whereas Atox1 was highly expressed in the disease group. We selected Atox1 for subsequent analysis. Transverse aortic constriction (TAC) method was applied for establishing a mouse model of HF-associated cardiac hypertrophy. In the model mice, we found significantly overexpressed Atox1 (fold change = 3.47) by qRT-PCR and increased levels of cuproptosis marker proteins SLC31A1 and FDX1 as well as Dlat aggregation. To further examine the action mechanism of Atox1, cardiomyocytes (H9c2) were treated with Ang II to simulate cardiac hypertrophy in vitro, followed by ATOX1 knockdown. It was found that low expression of Atox1 inhibited cuproptosis and suppressed cardiomyocyte hypertrophy. When cuproptosis was activated in Ang II + si-Atox1 group using elesclomol + CuCl

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