ArticleBiomaterials2016
Valve interstitial cell tensional homeostasis directs calcification and extracellular matrix remodeling processes via RhoA signaling.
Article in Biomaterials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- 3D Contractile and Remodeling Behaviors of Functionally Normal and Prolapsed Human Mitral Valve Interstitial Cells.Annals of biomedical engineering · 2026Article
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- 3D Contractile and Remodeling Behaviors of Functionally Normal and Prolapsed Human Mitral Valve Interstitial Cells.bioRxiv : the preprint server for biology · 2025Article
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- Biomechanical Remodeling of Aortic Valve Interstitial Cells During Calcified Lesion Formation In Vitro.Annals of biomedical engineering · 2024Article
- Nanocarriers of shRNA-Runx2 directed to collagen IV as a nanotherapeutic system to target calcific aortic valve disease.Materials today. Bio · 2023Article
- Reducing retraction in engineered tissues through design of sequential growth factor treatment.Biofabrication · 2023Article
- Glycosaminoglycans affect endothelial to mesenchymal transformation, proliferation, and calcification in a 3D model of aortic valve disease.Frontiers in cardiovascular medicine · 2022Article
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification.Science advances · 2021Article
- Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease.Circulation research · 2021Review
- Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow.Biomedicines · 2021Article
- Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro.Biomaterials · 2021Article
- On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology.Cardiovascular engineering and technology · 2021Review
- Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.Acta biomaterialia · 2021Article
- Bioorthogonal click chemistries enable simultaneous spatial patterning of multiple proteins to probe synergistic protein effects on fibroblast function.Biomaterials · 2020Article
- Inorganic phosphate-osteogenic induction medium promotes osteogenic differentiation of valvular interstitial cells via the BMP-2/Smad1/5/9 and RhoA/ROCK-1 signaling pathways.American journal of translational research · 2020Article
- Spatial Regulation of Valve Interstitial Cell Phenotypes within Three-Dimensional Micropatterned Hydrogels.ACS biomaterials science & engineering · 2019Article
- Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets.Frontiers in cardiovascular medicine · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsValve interstitial cells are active and aggressive players in aortic valve calcification, but their dynamic mediation of mechanically-induced calcific remodeling is not well understood. The goal of this study was to elucidate the feedback loop between valve interstitial cell and calcification mechanics using a novel three-dimensional culture system that allows investigation of the active interplay between cells, disease, and the mechanical valve environment. METHODS &
resultsWe designed and characterized a novel bioreactor system for quantifying aortic valve interstitial cell contractility in 3-D hydrogels in control and osteogenic conditions over 14 days. Interstitial cells demonstrated a marked ability to exert contractile force on their environment and to align collagen fibers with the direction of tension. Osteogenic environment disrupted interstitial cell contractility and led to disorganization of the collagen matrix, concurrent with increased αSMA, TGF-β, Runx2 and calcific nodule formation. Interestingly, RhoA was also increased in osteogenic condition, pointing to an aberrant hyperactivation of valve interstitial cells mechanical activity in disease. This was confirmed by inhibition of RhoA experiments. Inhibition of RhoA concurrent with osteogenic treatment reduced pro-osteogenic signaling and calcific nodule formation. Time-course correlation analysis indicated a significant correlation between interstitial cell remodeling of collagen fibers and calcification events.
conclusionsInterstitial cell contractility mediates internal stress state and organization of the aortic valve extracellular matrix. Osteogenesis disrupts interstitial cell mechanical phenotype and drives disorganization, nodule formation, and pro-calcific signaling via a RhoA-dependent mechanism.
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Registered trials
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