{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:20:58Z","timestamp":1780806058622,"version":"3.54.1"},"reference-count":30,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\nObjective:<\/jats:title>\nMyocardial ischemia\u2013reperfusion injury (MIRI) is a critical pathological basis for cardiovascular diseases. In recent years, the effect of ferroptosis on MIRI has attracted extensive attention. Vaspin, an adipose tissue-derived serine protease inhibitor, has multiple biological functions, including anti-inflammatory and antioxidant effects. This study aims to investigate the molecular mechanism by which vaspin alleviates MIRI by regulating hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and ferroptosis signaling pathways.<\/jats:p>\n<\/jats:sec>\n\nMaterial and Methods:<\/jats:title>\nA mouse model of myocardial ischemia\/reperfusion (I\/R) and a hypoxia\/reoxygenation (H\/R) model was used to evaluate the protective effects of vaspin on MIRI. The mechanism by which ferroptosis is modulated by the vaspin\/HIF-1\u03b1 signaling pathway was investigated by constructing a vaspin overexpression adenoviral vector. Myocardial infarct size and histological changes were assessed using triphenyltetrazolium chloride and hematoxylin\u2013eosin staining. Ferroptosis-related proteins were detected by Western blot assay, and apoptosis and reactive oxygen species levels were analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Iron content in myocardial tissue and cells was measured by enzyme-linked immunosorbent assay.<\/jats:p>\n<\/jats:sec>\n\nResults:<\/jats:title>\nMyocardial I\/R increased myocardial infarct size and serum lactate dehydrogenase (LDH) levels compared with the control group, indicating severe myocardial injury. Western blot results showed that MIRI reduced endogenous vaspin and HIF-1\u03b1 levels and inhibited glutathione peroxidase 4. In vivo<\/jats:italic> and in vitro<\/jats:italic> vaspin overexpression treatment reduced infarct size, decreased LDH levels, inhibited ferroptosis pathway activity, and alleviated oxidative stress levels in myocardial tissues. In the H\/R model, vaspin overexpression upregulated HIF-1\u03b1, inhibited ferroptosis markers, and reduced apoptosis and iron deposition. However, inhibiting HIF-1\u03b1 reversed the cardioprotective and anti-ferroptotic effects of vaspin.<\/jats:p>\n<\/jats:sec>\n\nConclusion:<\/jats:title>\nVaspin inhibits ferroptosis and upregulates the HIF-1\u03b1 signaling pathway to mitigate myocardial I\/R injury. The vaspin\/HIF-1\u03b1 pathway could be a potential target for MIRI prevention and treatment and offers fresh perspectives on ischemic heart disease management. Vaspin could be a novel cardioprotective agent that plays a significant role in the prevention and treatment of cardiovascular diseases.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/cytojournal_141_2024","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T09:40:16Z","timestamp":1734082816000},"page":"64","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Vaspin inhibits ferroptosis: A new hope for treating myocardial ischemia\u2013reperfusion injury"],"prefix":"10.25259","volume":"21","author":[{"given":"Xuehong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of General Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyun","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Three Departments of Heart Disease, 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