# Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target

## TL;DR

This review explores how ferroptosis, a type of cell death involving iron and lipids, contributes to heart disease and highlights new treatment possibilities.

## Contribution

The paper systematically characterizes ferroptosis mechanisms and evaluates therapeutic strategies for cardiovascular diseases.

## Key findings

- Ferroptosis plays a key role in atherosclerosis, heart failure, and cardiac remodeling.
- Emerging therapies include iron chelation, antioxidants, and GPX4 modulators.
- Biomarkers like lipid peroxidation products and non-coding RNAs are critical for clinical translation.

## Abstract

Ferroptosis, a regulated cell death modality driven by iron accumulation and lipid peroxidation, has emerged as a pivotal pathophysiological mechanism across a broad spectrum of cardiovascular diseases (CVDs), which remain the leading cause of global mortality. Although robust preclinical evidence indicates that modulation of ferroptosis attenuates myocardial and vascular injury, clinical translation is constrained by incomplete understanding of context-specific roles, the paucity of validated biomarkers, and the absence of targeted therapeutics with acceptable safety profiles. In this Review, we systematically characterizes the molecular architecture underlying ferroptosis, focusing on its core machinery governing iron homeostasis and lipid peroxidation, as well as the principal antioxidant defense systems that counteract this process. We subsequently survey the pathological contributions of ferroptosis across CVDs, detailing its involvement in atherosclerotic plaque instability, myocardial ischemia–reperfusion injury, heart failure progression, cardiomyopathies, and hypertensive cardiac remodeling. Furthermore, we evaluate emerging therapeutic strategies-ranging from iron chelation and radical-trapping antioxidants to GPX4-modulating agents and advanced nanomedicine-based delivery platforms-and critically appraise the landscape of candidate biomarkers indispensable for clinical translation, encompassing circulating lipid peroxidation products, iron metabolism indices, regulatory non-coding RNAs, and advanced imaging surrogates.By integrating mechanistic insights with translational perspectives, this Review positions ferroptosis as both a fundamental driver of cardiovascular pathology and a promising frontier for the development of precision diagnostics and targeted therapies aimed at mitigating the global burden of CVD.