ArticleScience advances2025
Y chromosome-linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Mosaic Loss-of-Y Chromosome in Men Is Associated With Aortic Enlargement But Not Aortic Stenosis.JACC. Advances · 2026Article
- Spatial and Single-Cell Mapping Reveals Valvular Interstitial Cell and Macrophage Sex Differences in Calcific Aortic Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Sex Differences in Lung Immunity.Immunological reviews · 2026Review
- Cardio-Vascular Extracellular Matrix: The Unmet Enigma.International journal of molecular sciences · 2026Review
- Fetal Bovine Serum Modulates Primary Human Cell Phenotypes, Endothelial Barrier Function, Vasculogenesis, and Angiogenesis in a Sex-Specific Manner.Cellular and molecular bioengineering · 2025Article
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Signals from the extracellular matrix: Region- and sex-specificity in cardiac aging.Current opinion in cell biology · 2025Review
- Determining sex differences in aortic valve myofibroblast responses to drug combinations identified using a digital medicine platform.Science advances · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
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10 authors.
Funding
Abstract
Aortic valve stenosis (AVS) is a progressive disease, wherein males more often develop valve calcification relative to females that develop valve fibrosis. Valvular interstitial cells (VICs) aberrantly activate to myofibroblasts during AVS, driving the fibrotic valve phenotype in females. Myofibroblasts further differentiate into osteoblast-like cells and produce calcium nanoparticles, driving valve calcification in males. We hypothesized that the lysine demethylase UTY (ubiquitously transcribed tetratricopeptide repeat containing Y-linked) decreases methylation uniquely in male VICs responding to nanoscale extracellular matrix cues to promote an osteoblast-like cell phenotype. Here, we describe a hydrogel biomaterial cell culture platform to interrogate how nanoscale cues modulate sex-specific methylation states in VICs activating to myofibroblasts and osteoblast-like cells. We found that UTY modulates the osteoblast-like cell phenotype in response to nanoscale cues uniquely in male VICs. Overall, we reveal a previously unidentified role of UTY in the regulation of calcification processes in males during AVS progression.
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