ArticleArteriosclerosis, thrombosis, and vascular biology2020
Secreted Factors From Proinflammatory Macrophages Promote an Osteoblast-Like Phenotype in Valvular Interstitial Cells.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 87 citations in OpenAlex.
- Bioprosthesis in aortic valve replacement: long-term inflammatory response and functionality.Open heart · 2022Trial
- Orthopedic surgery changes aortic valve composition inAtherosclerosis plus · 2026Article
- Bioactive 3D-Printed valve scaffold promoting valvular regeneration via immunomodulation and endothelialization.Bioactive materials · 2026Article
- Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.Animal models and experimental medicine · 2026Review
- Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.Molecular biology reports · 2026Review
- Single-nucleus and machine-learning integration identifies HLA-DRA and FTL as immune-metabolic axes and traditional Chinese medicine-targetable hubs in calcific aortic valve disease.Journal of computer-aided molecular design · 2026Article
- Gamma-Oryzanol Attenuates Aortic Valve Interstitial Cell Calcification via Suppression of BMP2-SMAD and MAPK Signaling Pathways.Biomolecules · 2026Article
- Circulating cytokines as triggers of endothelial dysfunction and sex-specific interstitial cell response in fibrocalcific aortic valve disease.International journal of biological sciences · 2026Article
- NETs accelerate aortic valve calcification by promoting M1 macrophage polarization through the TLR9 signaling pathway.Molecular and cellular biochemistry · 2025Article
- Immune Cell Dynamics in Cardiac Diseases: Insights From Single-Cell Sequencing.Journal of cellular and molecular medicine · 2025Review
- In vitro model assesses the susceptibility of polymeric scaffolds for material-driven heart valve regeneration to calcification.In vitro models · 2025Article
- PTEN Regulates Myofibroblast Activation in Valvular Interstitial Cells Based on Subcellular Localization.Advanced biology · 2025Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Y chromosome-linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.Science advances · 2025Article
- Engineering aortic valves via transdifferentiating fibroblasts into valvular endothelial cells without using viruses or iPS cells.Bioactive materials · 2025Article
- Valvular calcification in chronic kidney disease: new insights from recent clinical and preclinical studies.Clinical kidney journal · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- Novel Circulating Biomarkers in Aortic Valve Stenosis.International journal of molecular sciences · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveResident valvular interstitial cells (VICs) activate to myofibroblasts during aortic valve stenosis progression, which further promotes fibrosis or even differentiate into osteoblast-like cells that can lead to calcification of valve tissue. Inflammation is a hallmark of aortic valve stenosis, so we aimed to determine proinflammatory cytokines secreted from M1 macrophages that give rise to a transient VIC phenotype that leads to calcification of valve tissue. Approach and Results: We designed hydrogel biomaterials as valve extracellular matrix mimics enabling the culture of VICs in either their quiescent fibroblast or activated myofibroblast phenotype in response to the local matrix stiffness. When VIC fibroblasts and myofibroblasts were treated with conditioned media from THP-1-derived M1 macrophages, we observed robust reduction of αSMA (alpha smooth muscle actin) expression, reduced stress fiber formation, and increased proliferation, suggesting a potent antifibrotic effect. We further identified TNF (tumor necrosis factor)-α and IL (interleukin)-1β as 2 cytokines in M1 media that cause the observed antifibrotic effect. After 7 days of culture in M1 conditioned media, VICs began differentiating into osteoblast-like cells, as measured by increased expression of RUNX2 (runt-related transcription factor 2) and osteopontin. We also identified and validated IL-6 as a critical mediator of the observed pro-osteogenic effect.
conclusionsProinflammatory cytokines in M1 conditioned media inhibit myofibroblast activation in VICs (eg, TNF-α and IL-1β) and promote their osteogenic differentiation (eg, IL-6). Together, our work suggests inflammatory M1 macrophages may drive a myofibroblast-to-osteogenic intermediate VIC phenotype, which may mediate the switch from fibrosis to calcification during aortic valve stenosis progression.
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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.