Objective:

To summarize the mechanistic basis of endothelial ferroptosis under iron dyshomeostasis, focusing on specific pathways and their connection to microcirculatory injury during reperfusion.

Key Findings:

• Dysregulated iron handling during ischemia-reperfusion expands the labile iron pool, leading to ferroptosis in CMECs, characterized by specific biochemical changes.
• Ferroptotic CMECs weaken junctional integrity, increase edema, and exacerbate perfusion heterogeneity, contributing to overall myocardial injury.
• Inhibition of ferroptosis can partially restore endothelial function and improve microvascular perfusion, suggesting a therapeutic target.

Interpretation:

Ferroptosis in CMECs is a critical factor in microvascular dysfunction following myocardial ischemia-reperfusion, indicating that targeting this process may enhance recovery and improve clinical outcomes.

Limitations:

• Limited direct evidence and a unified mechanistic framework for CMEC ferroptosis, which may hinder the development of targeted therapies.
• Need for in vivo validation of CMEC-targeted interventions to confirm efficacy and safety.

Conclusion:

Addressing CMEC ferroptosis through targeted therapies may improve microvascular reperfusion and clinical outcomes in myocardial ischemia-reperfusion injury.