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Vascular smooth muscle cell (VSMC) loss is a critical pathological feature of TAD. Roxadustat (ROX), a HIF stabilizer for renal anemia, was evaluated in a \u03b2\u2010aminopropionitrile (BAPN)\u2010induced TAD mouse model. It significantly improved survival, attenuated weight loss and aortic dilation, decreased the incidence of TAD, alleviated elastic fibers damage, and ultimately inhibited TAD progression. Mechanistically, ROX upregulated HIF\u20101\u03b1 expression, reduced vascular wall iron deposition and lipid peroxidation products (MDA, 4\u2010HNE), and normalized aberrant expression of ferroptosis markers ACSL4, TFR1, GPX4 and FTH1. In\u00a0vitro, it mitigated Erastin\/Ang II\u2010induced VSMC ferroptosis, improved mitochondrial structure and function by enhancing oxygen consumption rate (OCR), restoring membrane potential, reducing reactive oxygen species (ROS), and boosting mitophagy via upregulating HIF\u20101\u03b1 and mitophagy markers (PINK1, Parkin). The HIF\u20101\u03b1 inhibitor KC7F2 and siHIF\u20101\u03b1 reversed these effects. Taken together, our findings demonstrate that ROX protects against TAD by promoting HIF\u20101\u03b1 expression to enhance mitophagy and inhibit VSMC ferroptosis, offering potential clinical implications for TAD prevention and treatment.<\/jats:p>","DOI":"10.1096\/fj.202600149r","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:20:31Z","timestamp":1779895231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Roxadustat Ameliorates Thoracic Aortic Dissection by Activating HIF\u20101\u03b1\u2010Mediated Mitophagy to Inhibit Ferroptosis"],"prefix":"10.1096","volume":"40","author":[{"given":"Dan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery The First Affiliated Hospital of Henan University, Henan University  Kaifeng 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