Ferroptosis-related gene dysregulation impairs aortic wall biomechanics and contributes to aortic dissection...

This study aimed to explore the association between smooth muscle cell (SMC) ferroptosis, aortic biomechanical properties, and the pathogenesis of aortic dissection (AD) across age groups to deepen mechanistic understanding. Assessments included immunohistochemistry for ferroptosis marker HMOX1, immunofluorescence for contractile SMC marker α-SMA, and uniaxial tensile testing. Results showed that the AD group had significantly higher HMOX1 expression and lower α-SMA expression across all age subgroups compared with controls. In AD, HMOX1 correlated positively with age, while α-SMA correlated negatively (no such correlations in controls). The AD group exhibited lower axial and circumferential failure stress than controls, with age-dependent directional variations: axial stress reduction dominated in the elderly, and circumferential reduction in the young. In AD, higher HMOX1 and lower α-SMA correlated with reduced axial stretch ratio. AD is characterized by enhanced SMC ferroptosis and loss of contractile SMCs, particularly in the elderly. Ferroptosis may reduce contractile cells via SMC phenotypic modulation, impairing aortic biomechanics, especially axially and increasing susceptibility to longitudinal intimal tearing. Age significantly influences ferroptosis severity and biomechanical failure patterns.