Related Experiment Video
Updated: May 29, 2026
05:47
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Spatial and Single-Cell Mapping Reveals Valvular Interstitial Cell and Macrophage Sex Differences in Calcific Aortic
Talia Baddour1,2, Van K Ninh1,3, Rayyan M Gorashi1,2
1Shu Chien-Gene Lay Department of Bioengineering (T.B., V.K.N., R.M.G., R.P., K.R.K., B.A.A.), University of California, San Diego, La Jolla.
Arteriosclerosis, Thrombosis, and Vascular Biology
|May 28, 2026
Summary
Sex differences in calcific aortic valve disease (CAVD) involve distinct cellular mechanisms. Males show increased calcification and AP-1 factors, while females exhibit elevated fibrosis and macrophage activity, impacting CAVD progression.
Area of Science:
- Cardiovascular Biology
- Translational Medicine
- Genomics
Background:
- Calcific aortic valve disease (CAVD) exhibits documented sex disparities in clinical progression to aortic valve stenosis.
- The cellular and molecular mechanisms underlying sex-dependent fibrocalcification in aortic valve tissue remain largely undefined.
Purpose of the Study:
- To investigate the sex-specific cellular and molecular mechanisms driving fibrocalcification in human aortic valve tissues.
- To elucidate the role of valvular interstitial cells (VICs) and macrophages in sex-dependent CAVD pathogenesis.
Main Methods:
- Histological analysis and scanning electron microscopy of human aortic valve tissues to quantify calcification.
- Single-cell and spatial transcriptomics to analyze VIC and macrophage gene expression and spatial organization near calcification sites.
- RNA in situ hybridization and bioinformatics for cell communication analysis to validate sex-dependent gene expression and interactions.
Main Results:
- Male CAVD valves showed greater calcification area and male-biased AP-1 transcription factor expression.
- Female CAVD valves displayed increased fibrosis, elevated SERPINE1 (PAI-1) expression, and distinct macrophage heterogeneity.
- Spatial transcriptomics revealed male-dependent COMP localization in VICs, contrasting with nonlocalized expression in females.
Conclusions:
- Significant sex differences exist in VIC and macrophage heterogeneity and function near calcification sites in aortic valve tissue.
- Sex-based transcriptomics analyses are crucial for understanding the cellular phenotypes driving sex differences in aortic valve fibrocalcification.
