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The bidirectional regulatory effect of TXNRD2 methylation in patients with chronic heart failure and its nonlinear

Ruonan Zhao1, Lin Ma1, Ruiping Wang2

  • 1School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, 712046, P. R. China.

Journal of Cardiothoracic Surgery
|June 4, 2025
PubMed

Insights

Chronic heart failure (CHF) involves altered TXNRD2 promoter methylation, with specific CpG sites showing decreased or increased levels. This epigenetic regulation may impact CHF progression and offers potential therapeutic targets.

Area of Science:

  • Epigenetics
  • Cardiovascular Medicine
  • Molecular Biology

Background:

  • Chronic heart failure (CHF) is a complex condition with incompletely understood molecular mechanisms.
  • Epigenetic modifications, such as DNA methylation, are increasingly recognized as key players in disease pathogenesis.
  • The thioredoxin reductase 2 (TXNRD2) gene is implicated in cellular redox balance and may play a role in cardiovascular health.

Purpose of the Study:

  • To investigate CpG methylation patterns in the TXNRD2 promoter region in patients with chronic heart failure (CHF).
  • To correlate TXNRD2 promoter methylation levels with clinical indicators of CHF severity and cardiac function.
  • To explore the potential of TXNRD2 methylation as a biomarker and therapeutic target for CHF.

Main Methods:

  • Analysis of whole blood samples from 20 CHF patients and 20 healthy controls.
  • Utilizing Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) to quantify CpG methylation.
  • Comparison of methylation levels in the TXNRD2-FA42 region across different patient groups.

Main Results:

  • Significant differences in TXNRD2 promoter methylation were observed between CHF patients and healthy controls.
  • Specifically, TXNRD2-FA42_CpG_3 methylation was found to be lower in CHF patients (P = 0.0407).
  • Conversely, TXNRD2-FA42_CpG_8 methylation was significantly higher in CHF patients compared to controls (P = 0.0183).

Conclusions:

  • TXNRD2 promoter methylation in CHF patients demonstrates bidirectional regulation, with distinct CpG sites showing opposing methylation changes.
  • These methylation alterations may influence critical physiological processes including coagulation, renal function, and blood cell counts.
  • The findings enhance the understanding of CHF pathogenesis at a molecular level and suggest novel avenues for therapeutic intervention.
Keywords:
Chronic heart failureDNA methylationSelenoprotein thioredoxin reductase 2 (TXNRD2)

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