Key result
Exercise serves as a promising modifier of cardiovascular ferroptosis rather than an established targeted therapy.
Why the study?
Whether exercise can modify ferroptosis-related vulnerability in the heart and vasculature remains an incompletely resolved question.
Does exercise training modulate ferroptosis-related cardiovascular injury in preclinical models and human clinical contexts?
Does exercise training modulate ferroptosis-related cardiovascular injury in preclinical models and human clinical contexts?
Exercise is a promising modifier of ferroptosis-related cardiovascular biology in preclinical models, but lacks direct evidence as a ferroptosis-targeted therapy in humans.
Exercise-ferroptosis links in cardiovascular injury remain unresolved; leaves open whether training alters iron-peroxidation vulnerability.
Ferroptosis connects disrupted iron handling, phospholipid peroxidation, and insufficient antioxidant defense with cardiovascular injury. Whether exercise can modify ferroptosis-related vulnerability in the heart and vasculature remains an important but incompletely resolved question. This mechanism-centered narrative review evaluates exercise-related evidence across cardiovascular injury contexts and distinguishes direct cardiovascular experiments from supportive marker studies, indirect mechanistic evidence, and human clinical contexts. PubMed was searched through June 2026, with supplementary retrieval from the Web of Science Core Collection and citation tracing. Among available exercise-specific studies, current evidence is most informative in preclinical models, particularly doxorubicin cardiotoxicity, where endurance exercise preconditioning has been linked to reduced iron accumulation, lipid-peroxide injury, mitochondrial damage, and myocardial dysfunction in studies incorporating ferroptosis-sensitive perturbation. Additional evidence from ischemia-reperfusion injury, diabetic cardiomyopathy, cardiac fibrosis, and experimental heart failure suggests that exercise may influence iron handling, the system Xc − –GSH–GPX4 axis, NRF2-related antioxidant regulation, lipid peroxidation, mitochondrial resilience, and inflammatory signaling. However, many studies remain marker-based, and evidence for resistance or combined training in tissue-level cardiovascular ferroptosis is limited. Human exercise studies provide translational context through improvements in vascular, metabolic, inflammatory, and oxidative-stress outcomes, but they do not yet establish ferroptosis modulation in cardiovascular tissue. Future studies require clearer exercise-dose reporting, serial sampling, tissue-level ferroptosis assays, pathway perturbation, clinically relevant models, and validated human biomarkers. Overall, exercise is best interpreted as a promising modifier of ferroptosis-related cardiovascular biology rather than an established ferroptosis-targeted therapy.
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Han et al. (2026) conducted a review in Ferroptosis-related cardiovascular injury. Exercise was evaluated. Exercise is best interpreted as a promising modifier of ferroptosis-related cardiovascular biology rather than an established ferroptosis-targeted therapy.
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