ArticleBiomaterials2014
The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation.
Article in Biomaterials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- From biomechanical mechanisms to clinical reasoning: Deciphering mechanobiological drivers of aortic valve calcification for precision therapy.Mechanobiology in medicine · 2026Review
- Advances in Pathophysiological Mechanisms of Degenerative Aortic Valve Disease.Cardiology research · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Biomechanical Remodeling of Aortic Valve Interstitial Cells During Calcified Lesion Formation In Vitro.Annals of biomedical engineering · 2024Article
- Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays.Science advances · 2024Article
- Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact.Interactive cardiovascular and thoracic surgery · 2022Article
- Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease.Antioxidants (Basel, Switzerland) · 2022Article
- Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling.JACC. Basic to translational science · 2022Article
- Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Journal of clinical medicine · 2022Review
- The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease.Biomedicines · 2022Review
- Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells.International journal of molecular sciences · 2022Article
- Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy.European heart journal · 2022Article
- Models and Techniques to Study Aortic Valve CalcificationFrontiers in pharmacology · 2022Review
- Single-cell RNA-sequencing analysis of aortic valve interstitial cells demonstrates the regulation of integrin signaling by nitric oxide.Frontiers in cardiovascular medicine · 2022Article
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- Valvular Endothelial Cell Response to the Mechanical Environment-A Review.Cell biochemistry and biophysics · 2021Review
- Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease.Circulation research · 2021Review
- Isolation of Human Primary Valve Cells for In vitro Disease Modeling.Journal of visualized experiments : JoVE · 2021Article
- Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro.Biomaterials · 2021Article
- Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.Acta biomaterialia · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC phenotype and nodule formation were tested using a co-culture platform with physiologically relevant matrix elasticities and diffusion distance. 100 μm thin poly(ethylene glycol) (PEG) hydrogels of 3-27 kPa Young's moduli were fabricated in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known to change significantly within this range, while VlvECs lined the underside of the membrane. Co-culture with VlvECs significantly reduced VIC activation to the myofibroblast phenotype on all gels with the largest percent decrease on the 3 kPa gels (~70%), while stiffer gels resulted in approximately 20-30% decrease. Additionally, VlvECs significantly reduced αSMA protein expression (~2 fold lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of nodules formed on the 27 kPa gels. Effects of VlvECs were prevented when nitric oxide (NO) release was inhibited with l-NAME, suggesting that VlvEC produced NO inhibits VIC activation. Withdrawal of l-NAME after 3, 5, and 7 days with restoration of VlvEC NO production for 2 additional days led to a partial reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC produced NO reduced VIC activation was studied by inhibiting initial and mid-stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK) with LPA, abolished VlvEC effects on VIC activation. This work contributes substantially to the understanding of the valve endothelium's role in preventing VIC functions associated with aortic valve stenosis initiation and 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.