{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:17:41Z","timestamp":1785233861117,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wan Fang Hospital, Taipei Medical University","award":["112-wf-eva-23"],"award-info":[{"award-number":["112-wf-eva-23"]}]},{"name":"Wan Fang Hospital, Taipei Medical University","award":["NSTC 112-2314-B-038-122-MY3"],"award-info":[{"award-number":["NSTC 112-2314-B-038-122-MY3"]}]},{"name":"National Science and Technology Council, Taiwan","award":["112-wf-eva-23"],"award-info":[{"award-number":["112-wf-eva-23"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NSTC 112-2314-B-038-122-MY3"],"award-info":[{"award-number":["NSTC 112-2314-B-038-122-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aortic dissection (AD) is a life-threatening vascular condition with limited pharmacological options, and shared risk factors with cardiac disease include hypertension, atherosclerosis, smoking, and dyslipidemia. This study investigated Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, in a BAPN\/Ang-II-induced mouse model of AD, revealing significant therapeutic potential. Fer-1 significantly reduced AD incidence and mortality by preserving aortic wall integrity. RNA sequencing identified 922 differentially expressed genes, with 416 upregulated and 506 downregulated. Bioinformatics analysis revealed that Fer-1 modulates key regulators, such as MEF2C and KDM5A, impacting immune responses, oxidative stress, apoptosis, and lipid metabolism. Additionally, Fer-1 alters miRNA expression, with the upregulation of miR-361-5p and downregulation of miR-3151-5p, targeting pathways involved in inflammation, oxidative stress, and smooth muscle cell (SMC) phenotypic stability. Functional pathway analysis highlighted the inhibition of actin cytoskeleton, ILK, and IL-17 signaling, essential for SMC differentiation and extracellular matrix remodeling. Gene interaction network analysis identified 21 central molecules, including CXCR3, ACACA, and BPGM, associated with lipid metabolism, inflammation, and vascular remodeling. This research elucidates the mechanism of ferroptosis in AD pathogenesis and establishes Fer-1 as a promising therapeutic intervention. AD and cardiac diseases share molecular mechanisms, risk factors, and pathological processes, positioning AD within the broader scope of cardiovascular pathology. By attenuating lipid peroxidation, oxidative stress, and inflammation, Fer-1 may have cardioprotective effects beyond AD, providing a foundation for future translational research in cardiovascular medicine.<\/jats:p>","DOI":"10.3390\/ijms26094338","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:44:23Z","timestamp":1746171863000},"page":"4338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptome Insights into Protective Mechanisms of Ferroptosis Inhibition in Aortic Dissection"],"prefix":"10.3390","volume":"26","author":[{"given":"Chun-Che","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-0888","authenticated-orcid":false,"given":"Chi-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Pin","family":"Chuu","sequence":"additional","affiliation":[{"name":"Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei 11221, Taiwan"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming Chiao-Tung University Hospital, Yilan 26058, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jung","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-0923","authenticated-orcid":false,"given":"Hsin-Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16053","DOI":"10.1038\/nrdp.2016.53","article-title":"Aortic dissection","volume":"2","author":"Nienaber","year":"2016","journal-title":"Nat. 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