Deep lipidomic profiling reveals sex dimorphism of lipid metabolism in fibro-calcific aortic valve disease

Abstract Fibro-calcific aortic valve disease (FCAVD) is the most common valvular heart disease manifesting in pathological fibro-calcific remodeling of the aortic valve (AV) leaflets, ultimately leading to aortic stenosis. Although lipid dysmetabolism is a driver of FCAVD pathogenesis, the molecular details of the AV lipidome remodeling upon fibrosis and calcification remain largely unknown. Here, we employed advanced lipidomics technologies for deep quantitative profiling of metabolic trajectories in human tricuspid and bicuspid AVs at different pathological stages. Specific extrinsic and intrinsic lipid trends, accompanying the development of fibrosis and calcification, were identified. Importantly, significant differences in lipid signatures between male and female individuals were demonstrated and were attributable to altered sphingolipid metabolism. Taken together, deep lipidomics profiling allowed to identify major molecular events and revealed a high extent of sex-dimorphism in lipidomics signatures of human FCAVD. Competing Interest Statement The authors have declared no competing interest. Data availability The data used for above mentioned plots can be accessed in corresponding GitHub code repositories from the LMAI team https://github.com/LMAI-TUD. The raw data/mzML spectra and processed lipidomics data can be accessed through Metabolomics Workbench ST003364 (doi: 10.21228/M8G24F)25.