Key result
Female sex is linked to greater sphingomyelin and ceramide accumulation in fibro-calcific aortic valve disease.
Why the study?
Although dyslipidemia is a driver of FCAVD pathogenesis, the precise lipidome-wide changes underlying AV fibrosis and calcification remain largely unknown.
Observational (n=55)
No
Should not yet change aortic valve disease management; leaves open sex-specific sphingolipid roles as therapeutic targets.
Fibro-calcific aortic valve disease (FCAVD) is the most common valvular heart disease manifesting in pathological remodeling of the aortic valve (AV) leaflets, ultimately leading to aortic stenosis. Although dyslipidemia is a driver of FCAVD pathogenesis, the precise lipidome-wide changes underlying AV fibrosis and calcification remain largely unknown. Here, we performed deep quantitative lipidomics to profile the metabolic trajectories in human tricuspid and bicuspid AVs, and found stage-dependent extrinsic and intrinsic lipid trends. Furthermore, lipids derived from infiltrating lipoproteins are further metabolized within the AV. Intrinsic lipid remodeling suggested tissue degeneration with a loss of phosphatidylserines. Surprisingly, male and female patients showed markedly different lipid signatures of FCAVD progression, with female patients accumulating significantly higher levels of sphingomyelins and ceramides. The high extent of sexual dimorphism in the valve lipidome strongly suggests that tailored approaches should be undertaken to enhance mechanistic insight and to facilitate pharmacological intervention for FCAVD.
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Prabutzki et al. (2025) conducted an observational in Fibro-calcific aortic valve disease (n=55). Lipidomics profiling vs. Male vs. female patients and disease stages was evaluated on Lipidomic signatures across disease progression stages. Female patients with fibro-calcific aortic valve disease accumulated significantly higher levels of sphingomyelins and ceramides during disease progression compared to male patients.
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