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Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling

James A Roberts1, Richard D Rainbow1,2, Parveen Sharma1,2

  • 1Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.

International Journal of Molecular Sciences
|April 13, 2023
PubMed

Insights

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway protects against cardiovascular disease. However, aging and certain drugs can disrupt NRF2, increasing heart toxicity and dysfunction.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cardiology

Background:

  • Cardiovascular diseases (CVDs) significantly increase morbidity and mortality.
  • Key pathophysiological factors include disrupted reactive oxygen species (ROS) signaling, iron homeostasis, and mitochondrial function.
  • The transcription factor NRF2 regulates cytoprotective genes against oxidative and xenobiotic stresses.

Purpose of the Study:

  • To review the role of NRF2 in cardiovascular health and disease.
  • To explore how NRF2 dysregulation impacts cardiotoxicity.
  • To discuss the implications of NRF2 modulation for cardiovascular conditions.

Main Methods:

  • Literature review of NRF2 signaling pathways.
  • Analysis of NRF2's role in oxidative stress and mitochondrial function.
  • Examination of NRF2's interaction with aging and drug-induced cardiotoxicity.

Main Results:

  • NRF2 activation shows potential in alleviating cardiotoxicity and CVD progression.
  • Aging and chemotherapeutics (e.g., anthracyclines) can impair NRF2 responses.
  • Dysregulated NRF2 compromises cardiovascular system resilience.

Conclusions:

  • NRF2 is a critical regulator of cardiovascular homeostasis and stress resistance.
  • Understanding NRF2 dynamics is crucial for developing strategies against cardiotoxicity.
  • Targeting NRF2 may offer therapeutic benefits for cardiovascular diseases.
Keywords:
NRF2ageingcardiotoxicitycardiovascular diseasedoxorubicin

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