Temporal regulation of genetic programs governing multiple cell death during myocardial ischemia-reperfusion injury

Qiuyu Pang1, Xiangmin Meng1, Zhenfang Zhou1

  • 1Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Genetics
|September 22, 2025
PubMed
Abstract

Insights

This study reveals that apoptosis occurs early in myocardial ischemia-reperfusion injury. Ferroptosis and necrosis become dominant cell death modes during later reperfusion periods, impacting heart damage.

Area of Science:

  • Cardiovascular Biology
  • Cell Death Mechanisms
  • Myocardial Infarction Research

Background:

  • Reperfusion is crucial for myocardial infarction (MI) treatment but induces cardiac damage.
  • Understanding cell death modes in ischemia-reperfusion (I/R) injury is vital, yet direct comparisons across reperfusion times are limited.

Purpose of the Study:

  • To investigate the relationship between distinct cell death patterns and varying reperfusion durations.
  • To compare the temporal dynamics of cell death categories in myocardial I/R injury.

Main Methods:

  • Analysis of public sequencing data to identify cell death patterns.
  • Evaluation of cell death timing in cellular and murine models across different reperfusion intervals (6h, 12h, 24h).

Main Results:

  • Apoptosis is observed early in I/R injury and persists with increased reperfusion time.
  • Autophagy and cuproptosis changes are prominent in the early reperfusion phase.
  • Ferroptosis and necrosis become the primary cell death forms during medium-to-long-term reperfusion.

Conclusions:

  • Apoptosis is an early event in reperfusion injury.
  • Ferroptosis, necrosis, and pyroptosis are critical in prolonged myocardial I/R injury.