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Journal article
Deciphering the Role of Ferroptosis in the Pathogenesis of Peripheral Artery Disease Myopathy
Biology (Basel, Switzerland), Vol.14(5), p.537
05/12/2025
PMID: 40427725
Web of Science ID: WOS:001496751200001
Abstract
This study investigates ferroptosis in the context of peripheral artery disease (PAD), a vascular disease characterized by atherosclerosis of the lower extremities. Muscle atrophy and increased oxidative stress are hallmarks of PAD and correlate with worse clinical outcomes. Given ferroptosis’ association with oxidative stress, we explored its role in PAD myopathy by examining gene and protein markers related to metabolic pathways implicated in ferroptosis using both human PAD patients and cultured myotubes. Intermittent claudication (IC) PAD patients, critical limb ischemia (CLI) PAD patients, and non-PAD controls were recruited for this study. Calf muscle biopsies were analyzed for gene expression using qPCR, and protein levels were determined by Western blotting. Cultured myotubes treated with the ferroptosis inducer erastin provided an in vitro comparison. Results demonstrated upregulation of ferroptosis markers such as lipid peroxidation and PTGS2 gene expression in the muscle of CLI PAD patients compared to controls. Increased expression of ferroptosis-related genes HMOX1, ACSL4, ELAVL1, and Beclin-1 was also observed. Protein analysis showed trends consistent with gene expression in some ferroptosis markers. The increase in ferroptosis markers in CLI PAD patients, particularly in iron metabolism and autophagy pathways, suggests ferroptosis contributes to PAD myopathy.
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- Title
- Deciphering the Role of Ferroptosis in the Pathogenesis of Peripheral Artery Disease Myopathy
- Publication Details
- Biology (Basel, Switzerland), Vol.14(5), p.537
- Resource Type
- Journal article
- Publisher
- MDPI; BASEL
- Number of pages
- 15
- Grant note
- National Institute on Aging of the National Institutes of HealthSan Antonio Medical Foundation
This work was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG064420 (P.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, the study was supported by the San Antonio Medical Foundation (P.K., D.M.).
- Copyright
- © 2025 the authors.
- Identifiers
- WOS:001496751200001; 99381359165606600
- Academic Unit
- Usha Kundu, MD College of Health; Public Health
- Language
- English