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Published on: September 23, 2014
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Dissecting sexual dimorphism in aortic valve stenosis by proteomics
Ana Grego1, Cláudia Sousa-Mendes1, Diana Martins1
1RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, 4200-319, Portugal.
Clinical Proteomics
|October 6, 2025
Summary
Proteomics reveals significant sex differences in aortic valve stenosis (AVS). Women exhibit more fibrosis, while men show increased calcification due to immune cell infiltration and less oxidative stress protection, guiding personalized AVS therapies.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Sex Differences in Disease
Background:
- Aortic valve stenosis (AVS) treatment is limited to valve replacement, with no effective pharmacotherapy.
- Sexual dimorphism in AVS, including fibrosis in women and calcification in men, hinders drug development.
- Understanding molecular differences between sexes is crucial for developing personalized AVS therapies.
Purpose of the Study:
- To characterize the sexual dimorphism in aortic valve stenosis (AVS) using a proteomics approach.
- To identify molecular targets for sex-specific AVS therapies.
Main Methods:
- Proteomic analysis of 50 surgically excised aortic valves (50% female) using LC-MS/MS.
- Bioinformatic analysis of differentially expressed proteins (DEPs) to assess their role in sexual dimorphism.
- Validation of DEPs using immunohistochemistry, qRT-PCR, and ELISA on an additional 30 valves.
Main Results:
- Quantified ~4,000 proteins, identifying 76 DEPs between sexes.
- Identified higher abundance of CD163, CD74, and NADPH oxidase-2 (NOX2) in men's valves, linked to lipoprotein binding and macrophage activation.
- Observed women-specific dysregulation of spliceosomal proteins, correlating with a pro-fibrotic phenotype and higher glutathione peroxidase-1/NOX2 ratio, indicating greater oxidative stress protection.
Conclusions:
- Proteomics confirms significant sexual dimorphism in AVS.
- Women exhibit increased fibrotic remodeling, while men show greater immune cell infiltration and reduced oxidative stress protection, favoring calcification.
- Identified potential molecular targets for sex-personalized AVS modulation.
