Dissecting Sexual Dimorphism in Aortic Valve Stenosis by Proteomics

Managing aortic valve stenosis (AVS) is challenging because of the lack of pharmacotherapies to halt/revert stenosis, deeming aortic valve replacement (AVR) the only effective treatment. AVS management is further confronted with staggering sexual dimorphism; women display more extensive fibrosis, while men present remarkably higher valve calcification. To accelerate the development of effective and sex-personalised pharmacotherapies, deeper molecular insights are needed. Hence, we aimed to characterise AVS sexual dimorphism using proteomics. Aortic valves were obtained from surgical AVR. Disease severity was assessed by echocardiography. Fifty valves (50% women) were homogenised, and the proteins were quantified by LC-MS/MS. The relevance of differentially expressed proteins (DEPs) in sexual dimorphism was appraised using protein-protein interaction (PPI) and functional enrichment analyses (FEA). DEPs were validated using immunohistochemistry, qRT-PCR and ELISA, with the aid of 30 additional independent valves.