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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\u2013reperfusion 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.<\/jats:p>","DOI":"10.1186\/s43556-026-00420-9","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:02:07Z","timestamp":1772928127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-5886","authenticated-orcid":false,"given":"Suli","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"420_CR1","doi-asserted-by":"publisher","unstructured":"Ga M, V F, Cjl M, Ga R. 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