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The Interplay of Programmed Cell Death Networks in Cardiovascular Diseases: Mechanisms and Therapeutic Opportunities

Yuruo He1,2, Xiayu Zhang1,2, Jinhui Duan1,2

  • 1School of Medicine, Northwest University, 710069 Xi'an, Shaanxi, China.

Reviews in Cardiovascular Medicine
|July 31, 2026
PubMed

Insights

Programmed cell death (PCD) pathways are key in cardiovascular diseases (CVDs). This review details cell-specific PCD, regulatory networks, and natural compounds, proposing precision therapies for CVDs.

Area of Science:

  • Cardiovascular Translational Medicine
  • Molecular Biology
  • Cell Death Pathways

Background:

  • Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, ferroptosis, and necroptosis, are integral to cardiovascular diseases (CVDs) like atherosclerosis and myocardial ischemia-reperfusion injury.
  • Understanding cell-type-specific PCD is crucial, as endothelial cells primarily exhibit pyroptosis and ferroptosis, while macrophages display diverse PCD modalities and complex interactions.

Purpose of the Study:

  • To review cell-type-specific PCD signatures in CVDs.
  • To summarize key regulatory pathways and natural compounds modulating PCD networks.
  • To identify clinical translation bottlenecks and propose innovative therapeutic strategies.

Main Methods:

  • Systematic review of literature on PCD pathways in cardiovascular diseases.
  • Analysis of cell-type-specific PCD mechanisms and regulatory networks.
  • Evaluation of natural compounds and delivery systems for therapeutic potential.

Main Results:

  • Endothelial cells predominantly undergo pyroptosis and ferroptosis; macrophages exhibit multiple PCD modalities.
  • Key regulatory pathways (e.g., Piezo1/NLRP3, Nrf2/HO-1/GPX4) and natural compounds (melatonin, Guizhitongluo Tablet) are identified.
  • Clinical translation challenges include nonspecific distribution and lack of biomarkers; solutions like targeted delivery and PTGS2 biomarker are proposed.

Conclusions:

  • PCD network dysregulation significantly contributes to CVD pathogenesis.
  • Targeted modulation of PCD pathways using natural compounds and advanced delivery systems offers therapeutic promise.
  • Developing pathway-specific biomarkers and targeted delivery systems is essential for advancing cardiovascular translational medicine.
Keywords:
apoptosisautophagycardiovascular diseasesferroptosisnecroptosisprogrammed cell deathpyroptosis

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