ArticleJournal of biomedical materials research. Part A2025
Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.
Article in Journal of biomedical materials research. Part A, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed.
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 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
- Recent advances in sex-specific reproductive microphysiological systems for the systematic evaluation of assisted reproductive technology.Materials today. Bio · 2026Review
- Advances in novel biomaterials for cardiovascular tissue engineering and regenerative medicine.PeerJ · 2026Review
- Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.Scientific reports · 2025Article
- Fetal Bovine Serum Modulates Primary Human Cell Phenotypes, Endothelial Barrier Function, Vasculogenesis, and Angiogenesis in a Sex-Specific Manner.Cellular and molecular bioengineering · 2025Article
- Toward Sex-Specific Biomaterials Innovation: A Perspective.ACS biomaterials science & engineering · 2025Review
- 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
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Patients with aortic valve stenosis (AVS) experience fibrosis and/or calcification in valve tissue, which leads to heart failure if left untreated. Inflammation is a hallmark of AVS, and secreted cytokines from pro-inflammatory macrophages are thought to contribute to valve fibro-calcification by driving the activation of valvular interstitial cells (VICs) to myofibroblasts. However, the molecular mechanisms by which inflammatory cytokines differentially regulate myofibroblast activation as a function of biological sex are not fully defined. Here, we developed an in vitro hydrogel culture platform to culture male and female valvular interstitial cells (VICs) and characterize the sex-specific effects of inflammatory cytokines on VIC activation to myofibroblasts and osteoblast-like cells. Our data reveal that tumor necrosis factor alpha (TNF-α) modulates female-specific myofibroblast activation via MAPK/ERK signaling, nuclear chromatin availability, and osteoblast-like differentiation via RUNX2 nuclear localization. In parallel, our data also suggest that male-specific myofibroblast deactivation in response to TNF-α occurs via alternative pathways outside of MAPK/ERK signaling. Collectively, hydrogel biomaterials as cell culture platforms are critical for distinguishing sex differences in cellular phenotypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.