Analyzing the impact of ferroptosis on atherosclerotic plaque formation through biomechanical modeling

  • Ru Du The First College of Clinical Medical Science, China Three Gorges University, Yichang 443000, China
  • Yuhong Zuo The First College of Clinical Medical Science, China Three Gorges University, Yichang 443000, China
  • Xinan Wang The First College of Clinical Medical Science, China Three Gorges University, Yichang 443000, China
  • Jiawang Ding The First College of Clinical Medical Science, China Three Gorges University, Yichang 443000, China
DOI: https://doi.org/10.62617/mcb825
Keywords: atherosclerosis; ferroptosis; biomechanics; plaque stability; stress analysis; iron metabolism; cardiovascular disease; mechanical modeling
Article ID: 825

Abstract

Atherosclerotic plaque rupture, a primary cause of acute cardiovascular events, is fundamentally influenced by biomechanical forces. While ferroptosis, an iron-dependent form of regulated cell death, has been implicated in atherosclerosis progression, its impact on plaque biomechanics and stability remains poorly understood. We developed a comprehensive biomechanical model integrating ferroptotic parameters with plaque structural mechanics. Human carotid endarterectomy specimens (n = 45) were analyzed using a multi-modal approach combining mechanical testing, molecular analysis, and computational modeling. Plaque samples were categorized into stable (n = 15), vulnerable (n = 15), and transitional (n = 15) groups. Changes in mechanical properties, ferroptotic markers, and stress distributions were assessed over 72 h under controlled conditions. Ferroptosis induction resulted in significant alterations of plaque biomechanics. Peak circumferential stress in the fibrous cap increased from 142.3 ± 12.4 kPa to 286.4 ± 22.7 kPa (p < 0.001), while cap thickness decreased from 165.4 ± 12.3 μm to 98.6 ± 18.4 μm (p < 0.001). The iron accumulation showed a strong negative correlation with plaque stability (r = −0.892, p < 0.001). Mechanical testing revealed a 56.5% reduction in tensile strength and a 52.3% decrease in strain at failure in vulnerable plaques. Sensitivity analysis identified fibrous cap thickness (NSC = 0.924) and iron concentration (NSC = 0.856) as critical determinants of plaque stability. Our findings establish ferroptosis as a significant mediator of plaque biomechanical deterioration. The strong correlations between ferroptotic markers and mechanical instability suggest that targeting ferroptotic pathways may provide novel approaches for maintaining plaque stability. This study provides a quantitative framework for understanding the mechanical consequences of ferroptosis in atherosclerotic disease progression and identifies potential therapeutic targets for plaque stabilization.

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Published
2025-02-11
How to Cite
Du, R., Zuo, Y., Wang, X., & Ding, J. (2025). Analyzing the impact of ferroptosis on atherosclerotic plaque formation through biomechanical modeling. Molecular & Cellular Biomechanics, 22(2), 825. https://doi.org/10.62617/mcb825
Issue
Vol. 22 No. 2 (2025)
Section
Article

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