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Targeting Ferroptosis and Pyroptosis in Cardiovascular Diseases: Mechanisms and Therapeutic Implication

Wenjuan Zhang1,2, Kexin Zhang1,2, Wei Xu3

  • 1Department of Endocrinology and Metabolism, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, China.

Journal of Cardiovascular Translational Research
|June 13, 2026
PubMed

Insights

Cardiovascular diseases are driven by ferroptosis and pyroptosis, interconnected cell death pathways. Targeting these pathways, particularly with natural compounds, offers a promising strategy for precise cardiovascular therapy.

Area of Science:

  • Cardiovascular Medicine
  • Cellular Biology
  • Immunology

Background:

  • Cardiovascular diseases (CVDs) are the leading cause of death globally.
  • Current treatments partially address cardiomyocyte loss and remodeling.
  • Ferroptosis (iron-dependent cell death) and pyroptosis (inflammasome-driven cell death) are emerging key drivers of cardiovascular dysfunction and heart failure.

Purpose of the Study:

  • To synthesize current knowledge on the crosstalk between ferroptosis and pyroptosis in cardiovascular diseases.
  • To highlight the role of metabolic-immune coupling in these processes.
  • To explore natural products as potential therapeutic agents targeting both pathways.

Main Methods:

  • Literature synthesis focusing on the mechanistic links between ferroptosis and pyroptosis.
  • Emphasis on key molecular players like GPX4, ACSL4, NLRP3, and GSDMD.
  • Review of natural products (quercetin, paeoniflorin, curcumin) as dual regulators.

Main Results:

  • Ferroptosis and pyroptosis are mechanistically interconnected, influencing myocardial injury, vascular dysfunction, and heart failure.
  • Lipid peroxidation and ROS can activate the NLRP3 inflammasome, while gasdermin release impacts iron homeostasis.
  • Natural products show potential in activating protective pathways (Nrf2-GPX4) and suppressing inflammasomes.

Conclusions:

  • Targeting the crosstalk between ferroptosis and pyroptosis presents a novel therapeutic avenue for cardiovascular diseases.
  • Dual blockade of oxidative and inflammatory cell death mechanisms holds promise for precise cardiovascular therapy.
  • Further translational research is needed to optimize intervention timing and compound availability.

Keywords:
Cardiovascular diseasesFerroptosisHerbal monomersInflammationOxidative stressPyroptosis

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