ArticleAPL bioengineering2018
FGF-2 inhibits contractile properties of valvular interstitial cell myofibroblasts encapsulated in 3D MMP-degradable hydrogels.
Article in APL bioengineering, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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
26 citing papers in PubMed, 35 citations in OpenAlex.
- Matrix degradation promotes fibronectin deposition and spatial remodeling in 3D.Cell reports. Physical science · 2026Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- The Influence of Sulfation Degree of Glycosaminoglycan-Functionalized 3D Collagen I Networks on Cytokine Profiles of In Vitro Macrophage-Fibroblast Cocultures.Gels (Basel, Switzerland) · 2024Article
- Pathogenic Roles of Cardiac Fibroblasts in Pediatric Dilated Cardiomyopathy.Journal of the American Heart Association · 2023Article
- The effects of strain history on aortic valve interstitial cell activation in a 3D hydrogel environment.APL bioengineering · 2023Article
- Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation.Biomaterials science · 2022Article
- 4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling.Bioengineering & translational medicine · 2022Article
- Anti-fibrotic effects of pharmacologic FGF-2: a review of recent literature.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts.Nature biomedical engineering · 2021Article
- Engineering the aortic valve extracellular matrix through stages of development, aging, and disease.Journal of molecular and cellular cardiology · 2021Review
- Matters of the heart: Cellular sex differences.Journal of molecular and cellular cardiology · 2021Review
- Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity.Biomedicines · 2021Article
- Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics.Nature communications · 2021Article
- Tumor necrosis factor-α promotes and exacerbates calcification in heart valve myofibroblast populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology.Cardiovascular engineering and technology · 2021Review
- Prognostic Utility of Circulating Growth Factors in Aortic Valve Stenosis: A Pilot Study.Medicina (Kaunas, Lithuania) · 2021Article
- Dissecting Calcific Aortic Valve Disease-The Role, Etiology, and Drivers of Valvular Fibrosis.Frontiers in cardiovascular medicine · 2021Review
- Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.Acta biomaterialia · 2021Article
- Biology and Biomechanics of the Heart Valve Extracellular Matrix.Journal of cardiovascular development and disease · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Valvular interstitial cells (VICs) are responsible for the maintenance of the extracellular matrix in heart valve leaflets and, in response to injury, activate from a quiescent fibroblast to a wound healing myofibroblast phenotype. Under normal conditions, myofibroblast activation is transient, but the chronic presence of activated VICs can lead to valve diseases, such as fibrotic aortic valve stenosis, for which non-surgical treatments remain elusive. We monitored the porcine VIC response to exogenously delivered fibroblast growth factor 2 (FGF-2; 100 ng/ml), transforming growth factor beta 1 (TGF-β1; 5 ng/ml), or a combination of the two while cultured within 3D matrix metalloproteinase (MMP)-degradable 8-arm 40 kDa poly(ethylene glycol) hydrogels that mimic aspects of the aortic valve. Here, we aimed to investigate VIC myofibroblast activation and subsequent contraction or the reparative wound healing response. To this end, VIC morphology, proliferation, gene expression related to the myofibroblast phenotype [alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF)] and matrix remodeling [collagens (COL1A1 and COL3) and MMP1], and contraction assays were used to quantify the cell response. Treatment with FGF-2 resulted in increased cellular proliferation while reducing the myofibroblast phenotype, as seen by decreased expression of CTGF and α-SMA, and reduced contraction relative to untreated control, suggesting that FGF-2 encourages a reparative phenotype, even in the presence of TGF-β1. TGF-β1 treatment predictably led to an increased proportion of VICs exhibiting the myofibroblast phenotype, indicated by the presence of α-SMA, increased gene expression indicative of matrix remodeling, and bulk contraction of the hydrogels. Functional contraction assays and biomechanical analyses were performed on VIC encapsulated hydrogels and porcine aortic valve tissue explants to validate these findings.
Identifiers
What OpenQuestion holds
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.