Ferroptosis: key regulatory pathways and their implications in cardiovascular pathophysiology

Area of Science:

• Cardiovascular Research
• Cell Death Mechanisms
• Metabolomics

Background:

• Cardiovascular diseases (CVDs) are a major global health issue.
• Ferroptosis, an iron-dependent cell death pathway involving lipid peroxidation, is increasingly recognized in CVD pathogenesis.
• Understanding ferroptosis's molecular drivers and role in CVD is crucial for developing new treatments.

Purpose of the Study:

• To review the molecular mechanisms of ferroptosis in cardiovascular diseases.
• To explore the role of ferroptosis in various cardiovascular pathologies.
• To discuss the application of spatial metabolomics and therapeutic strategies targeting ferroptosis.

Main Methods:

• Comprehensive literature review of ferroptosis and cardiovascular diseases.
• Analysis of molecular drivers: iron metabolism, GPX4, Nrf2, AMPK, p53.
• Exploration of organelle roles (mitochondria, lysosomes, ER) in ferroptosis.
• Inclusion of spatial metabolomics as an analytical tool.
• Discussion of therapeutic interventions targeting ferroptosis.

Main Results:

• Ferroptosis is driven by dysregulated iron metabolism, GPX4 inactivation, and redox imbalance.
• Subcellular organelles critically regulate ferroptotic signaling.
• Ferroptosis contributes to atherosclerosis, heart failure, ischemia-reperfusion injury, and other CVDs.
• Spatial metabolomics offers insights into the spatiotemporal dynamics of ferroptosis in CVDs.

Conclusions:

• Ferroptosis is a key mechanism in cardiovascular disease progression.
• Targeting ferroptosis pathways presents a promising therapeutic avenue for CVDs.
• Further research, aided by spatial metabolomics, is needed for precision CVD interventions.