Ferroptosis in heart failure: from molecular insights to therapeutic implications

作者：Konstantinos Karampinos, Dimitrios Farmakis, Rijan Gurung, Roger S-Y Foo, Gerasimos Filippatos, Dennis V Cokkinos · 发表于：Cardiovascular Research · 年份：2026 · DOI：10.1093/cvr/cvag019 · 被引用次数：11 · 研究领域：Ferroptosis and cancer prognosis、GDF15 and Related Biomarkers、Clusterin in disease pathology

Ferroptosis is the form of regulated cell death driven by iron-induced lipid peroxidation, implicated in different cardiovascular diseases and especially heart failure. It is an abundant form of regulated cell death in the myocardium of many heart failure animal models, including the chronic ischaemic, pressure overload, diabetic, septic, obesity-related and doxorubicin-induced cardiomyopathy models. Across these models, disordered iron handling, antioxidant failure, enzymatic phospholipid peroxidation, and mitochondrial stress converge on ferroptosis, leading to contractile dysfunction and adverse remodelling. Although definitive causality between ferroptosis and heart failure has not yet been established, emerging evidence suggests that ferroptosis contributes to heart failure progression, supported by multi-layer rescue with classic inhibitors (ferrostatin-1, liproxstatin-1, iron chelators) and by cardiometabolic drugs with clinical efficacy in heart failure (sodium-glucose cotransporter 2 inhibitors, sacubitril/valsartan, finerenone, levosimendan, nicorandil) as well as polyphenols, which restore systolic and/or diastolic indices and reverse remodelling. Early human evidence aligns, showing that human failing myocardial and epicardial adipose tissue exhibit ferroptosis-specific transcriptional and lipidomic signatures, while circulating biomarkers and tissue profiles of patients receiving SGLT2 inhibitors indicate reduced ferroptosis activity. In this review, through crit...