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Transcriptome Insights into Protective Mechanisms of Ferroptosis Inhibition in Aortic Dissection
Chun-Che Shih1,2,3, Chi-Yu Chen4, Chih-Pin Chuu5
1Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
International Journal of Molecular Sciences
|May 14, 2025
Summary
Ferrostatin-1 (Fer-1) shows promise in treating aortic dissection (AD) by reducing incidence and mortality. This ferroptosis inhibitor preserves aortic integrity and impacts key molecular pathways, offering potential cardiovascular benefits.
Area of Science:
- Vascular Biology
- Pharmacology
- Cardiovascular Medicine
Background:
- Aortic dissection (AD) is a critical vascular condition with few treatment options.
- Shared risk factors link AD with cardiovascular diseases, including hypertension and dyslipidemia.
- Ferroptosis, a regulated cell death pathway, is implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the therapeutic potential of Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, in a mouse model of AD.
- To elucidate the molecular mechanisms underlying Fer-1's effects on AD.
- To explore Fer-1's potential broader cardiovascular protective effects.
Main Methods:
- Utilized a BAPN/Ang-II-induced mouse model to study AD.
- Administered Fer-1 to assess its impact on AD incidence, mortality, and aortic integrity.
- Performed RNA sequencing and bioinformatics analyses to identify differentially expressed genes and pathways.
- Analyzed miRNA expression profiles and gene interaction networks.
Main Results:
- Fer-1 significantly reduced AD incidence and mortality, preserving aortic wall integrity.
- Identified 922 differentially expressed genes, with key regulators like MEF2C and KDM5A modulated by Fer-1.
- Observed alterations in miRNA expression (miR-361-5p, miR-3151-5p) and inhibition of pathways crucial for smooth muscle cell function.
- Gene network analysis highlighted central molecules involved in lipid metabolism, inflammation, and vascular remodeling.
Conclusions:
- Fer-1 demonstrates significant therapeutic potential for aortic dissection by targeting ferroptosis.
- Fer-1 modulates critical molecular pathways, including immune response, oxidative stress, and lipid metabolism.
- Fer-1 may offer broader cardioprotective effects, warranting further translational research in cardiovascular medicine.
