ArticleBiomaterials2021
Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro.
Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- miR-138-5p Inhibits Aortic Valve Interstitial by Targeting SLC39A14 and Activating Nrf2 Signaling.Journal of biochemical and molecular toxicology · 2026Article
- Valve biology and rheumatic heart disease pathogenesis.Nature cardiovascular research · 2026Review
- Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a narrative review.Cardiovascular diagnosis and therapy · 2026Review
- Precision RNA interference of Smad3 and Runx2 via dual targeting nanocarriers mitigates aortic valve disease.Journal of translational medicine · 2026Article
- Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells.BBA advances · 2026Article
- Bioprosthetic heart valve degeneration: new insights into structural remodeling and calcification.Frontiers in cardiovascular medicine · 2026Review
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- Inflammation via JAK-STAT/HIF-1α Drives Metabolic Changes in Pentose Phosphate Pathway and Glycolysis That Support Aortic Valve Cell Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- 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
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling.JACC. Basic to translational science · 2023Article
- Strategies for Development of Synthetic Heart Valve Tissue Engineering Scaffolds.Progress in materials science · 2023Article
- Three-Dimensional Bioprinting of Ovine Aortic Valve Endothelial and Interstitial Cells for the Development of Multicellular Tissue Engineered Tissue Constructs.Bioengineering (Basel, Switzerland) · 2023Article
- Dantrolene inhibits lysophosphatidylcholine-induced valve interstitial cell calcific nodule formationFrontiers in cardiovascular medicine · 2023Article
- Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging.Nature communications · 2022Article
- Chondroitin Sulfate Promotes Interstitial Cell Activation and Calcification in an In Vitro Model of the Aortic Valve.Cardiovascular engineering and technology · 2022Article
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- Role of Runx2 in Calcific Aortic Valve Disease in Mouse Models.Frontiers in cardiovascular medicine · 2021Article
- The Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCalcific aortic valve disease (CAVD) is an actively regulated degenerative disease process. Clinical lesions exhibit marked 3D complexity not represented in current in vitro systems. We here present a unique mechanically stressed 3D culture system that recapitulates valve interstitial cell (VIC) induced matrix calcification through myofibroblastic activation and osteoblastic differentiation. We test the hypothesis that valve endothelial (VEC) - interstitial collaborative interactions modulate the risk and complexity of calcific pathogenesis within mechanically stressed and pro-inflammatory environments. APPROACH AND
resultsPorcine aortic valve endothelial and interstitial cells (VEC and VIC) were seeded in a mechanically constrained collagen hydrogels alone or in co-culture configurations. Raised 3D VIC-filled lesions formed within 7 days when cultured in osteogenic media (OGM), and surprisingly exacerbated by endothelial coculture. We identified a spatially coordinated pro-endochondral vs. pro-osteogenic signaling program within the lesion. VEC underwent Endothelial-to-Mesenchymal Transformation (EndMT) and populated the lesion center. The spatial complexity of molecular and cellular signatures of this 3D in vitro CAVD system were consistent with human diseased aortic valve histology. SNAI1 was highly expressed in the VEC and subendothelial direct VIC corroborates with human CAVD lesions. Spatial distribution of Sox9 vs. Runx2 expression within the developed lesions (Sox9 peri-lesion vs. Runx2 predominantly within lesions) mirrored their expression in heavily calcified human aortic valves. Finally, we demonstrate the applicability of this platform for screening potential pharmacologic therapies through blocking the canonical NFκB pathway via BAY 11-7082.
conclusionsOur results establish that VEC actively induce VIC pathological remodeling and calcification via EndMT and paracrine signaling. This mechanically constrained culture platform enables the interrogation of accelerated cell-mediated matrix remodeling behavior underpinned by this cellular feedback circuit. The high fidelity of this complex 3D model system to human CAVD mechanisms supports its use to test mechanisms of intercellular communication in valves and their pharmacological control.
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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.