Valvular & structural heart disease
Ferroptosis promotes aortic stenosis through 5-lipoxygenase
Authors' conclusion
These findings establish the ALOX5-ACSL4 axis as a critical mediator of ferroptosis in CAVD and promising repurposing target for clinical intervention.
Study context
- Population
- Calcified aortic valves from surgical patients; mouse models; SCAPIS and UK Biobank participants212 aortic valves
Methodological detailshuman valve tissue and valvular interstitial cell (VIC) models, mouse models, population cohorts (SCAPIS, UK Biobank)
- Human valve tissue and VIC models
- Mouse models
- Population cohorts (SCAPIS, UK Biobank)
Main finding
As reported in the abstract
- Intra-leaflet haemorrhage prevalent in calcified valves; correlated positively with calcification and circulating ferroptosis biomarker
- Lipid peroxidation centred on ALOX5 identified as dominating valvular ferroptosis pathway
- Ferroptosis in VIC triggered lipid peroxidation and calcification and reduced viability; reversed by targeting ALOX5-ACSL4 axis
- Doxorubicin-induced valvular ferroptosis exacerbated valvular thickening in apoE-/- mice via ALOX5-ACSL4 upregulation
- ALOX5 inhibition reduced valve thickness and haemodynamically improved valve function (wire injury model)
- Arachidonic acid levels independently predicted aortic valve calcification (SCAPIS) and incident AS (UK Biobank); positively correlated with circulating ferroptotic marker
Original publication
Ferroptosis promotes aortic stenosis through 5-lipoxygenase. Eur Heart J. Published 2 June 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →