ArticleBMC cardiovascular disorders2014
Manipulation of valve composition to elucidate the role of collagen in aortic valve calcification.
Article in BMC cardiovascular disorders, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Extracellular matrix remodeling in calcific aortic valve disease: Localized enrichment of type III collagen and LTBP-4.Matrix biology plus · 2026Article
- Nano-mechanical mapping of human and porcine abdominal aortic aneurysm.Journal of the mechanical behavior of biomedical materials · 2026Article
- Osteopontin-expressing valvular interstitial cell subpopulation as a driver of extracellular matrix remodeling in aortic valve disease.Frontiers in cardiovascular medicine · 2026Article
- Spatiotemporal Atlas of Heart Development Reveals Blood-Flow-Dependent Cellular, Structural, Metabolic, and Spatial Remodeling.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of osteopontin-stabilized amorphous calcium phosphate calcification in benign and pre-malignant breast disease.Scientific reports · 2025Article
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- Predictive value of valvular calcification for the recurrence of persistent atrial fibrillation after radiofrequency catheter ablation.Clinical cardiology · 2024Article
- The Role of Apoptosis and Oxidative Stress in a Cell Spheroid Model of Calcific Aortic Valve Disease.Cells · 2023Article
- The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy.Acta pharmaceutica Sinica. B · 2023Review
- Cellular-scale sex differences in extracellular matrix remodeling by valvular interstitial cells.Heart and vessels · 2023Article
- The tyrosine kinase inhibitor nilotinib targets the discoidin domain receptor DDR2 in calcific aortic valve stenosis.British journal of pharmacology · 2022Article
- Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells.International journal of molecular sciences · 2022Article
- Engineering the aortic valve extracellular matrix through stages of development, aging, and disease.Journal of molecular and cellular cardiology · 2021Review
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- Multiple functions of autophagy in vascular calcification.Cell & bioscience · 2021Review
- Extracellular Matrix in Calcific Aortic Valve Disease: Architecture, Dynamic and Perspectives.International journal of molecular sciences · 2021Review
- High Glucose Induced Changes in Human VEC Phenotype in a 3D Hydrogel Derived From Cell-Free Native Aortic Root.Frontiers in cardiovascular medicine · 2021Article
- Mechanical Regulation of Apoptosis in the Cardiovascular System.Annals of biomedical engineering · 2021Review
- 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
4 authors.
Funding
Abstract
backgroundExtracellular matrix (ECM) disarray is found in calcific aortic valvular disease (CAVD), yet much remains to be learned about the role of individual ECM components in valvular interstitial cell (VIC) function and dysfunction. Previous clinical analyses have shown that calcification is associated with decreased collagen content, while previous in vitro work has suggested that the presence of collagen attenuates the responsiveness of VICs to pro-calcific stimuli. The current study uses whole leaflet cultures to examine the contributions of endogenous collagen in regulating the phenotype and calcification of VICs.
methodsA "top-down" approach was used to characterize changes in VIC phenotype in response to collagen alterations in the native 3D environment. Collagen-deficient leaflets were created via enzymatic treatment and cultured statically for six days in vitro. After culture, leaflets were harvested for analysis of DNA, proliferation, apoptosis, ECM composition, calcification, and gene/protein expression.
resultsIn general, disruption of collagen was associated with increased expression of disease markers by VICs in whole organ leaflet culture. Compared to intact control leaflets, collagen-deficient leaflets demonstrated increased VIC proliferation and apoptosis, increased expression of disease-related markers such as alpha-smooth muscle actin, alkaline phosphatase, and osteocalcin, and an increase in calcification as evidenced by positive von Kossa staining.
conclusionsThese results indicate that disruption of the endogenous collagen structure in aortic valves is sufficient to stimulate pathological consequences in valve leaflet cultures, thereby highlighting the importance of collagen and the valve extracellular matrix in general in maintaining homeostasis of the valve phenotype.
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