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NRF2-Targeted Therapy in Cardiovascular Disease Transitions from Systemic Activation to Precision Redox Medicine

Yizhao Peng1, Jinhong Wei1, Yang Yang1

  • 1School of Life Sciences and Medicine, Northwest University, Xi'an 710069, China.

Antioxidants (Basel, Switzerland)
|February 27, 2026
PubMed

Insights

Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) protects the heart from oxidative stress. While promising in early studies, clinical application faces challenges requiring new strategies for safe and effective use.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Redox Homeostasis

Background:

  • Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is crucial for cellular defense against oxidative stress and cardiac remodeling.
  • NRF2 activation preserves mitochondrial function, protein stability, and inhibits cell death pathways like necroptosis and ferroptosis.

Purpose of the Study:

  • To review the NRF2-KEAP1 axis in cardiovascular diseases.
  • To assess NRF2's efficacy in ischemia-reperfusion injury and diabetic cardiomyopathy.
  • To evaluate pharmacological strategies and delivery innovations for clinical translation.

Main Methods:

  • Review of molecular mechanisms of the NRF2-KEAP1 pathway.
  • Synthesis of preclinical and clinical evidence for NRF2 in cardiovascular conditions.
  • Analysis of pharmacological approaches, including protein-protein interaction inhibitors and targeted delivery systems.

Main Results:

  • NRF2 plays a significant role in mitigating cardiac damage from oxidative stress.
  • Preclinical efficacy of NRF2 activation contrasts with clinical translation challenges.
  • Indiscriminate NRF2 activation presents safety concerns, necessitating refined therapeutic strategies.

Conclusions:

  • Targeting the NRF2 pathway holds therapeutic potential for cardiovascular diseases.
  • Overcoming clinical limitations requires innovative strategies like cardiac-specific delivery and biomarkers.
  • Rigorous validation is essential to ensure the safety and efficacy of NRF2-based therapies.
Keywords:
NRF2cardiac remodelingheart failureoxidative stressprecision redox medicine

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