ArticleProceedings of the National Academy of Sciences of the United States of America2018
Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Engineered tissues and strategies to overcome challenges in drug development.Advanced drug delivery reviews · 2020Pooled it
- Pathology-tailored nanotherapy via Galectin-3-targeted and triple-responsive nanoparticles enables multimodal therapy against aortic dissection.Journal of nanobiotechnology · 2026Article
- Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.Scientific reports · 2025Article
- Y chromosome-linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.Science advances · 2025Article
- Oxidative low-density lipoprotein and shear induced calcification within a calcific aortic valve disease-on-a-chip platform.Frontiers in cardiovascular medicine · 2025Article
- Needle-induced cavitation: A method to probe the local mechanics of brain tissue.Journal of the mechanical behavior of biomedical materials · 2024Article
- A three-dimensional valve-on-chip microphysiological system implicates cell cycle progression, cholesterol metabolism and protein homeostasis in early calcific aortic valve disease progression.Acta biomaterialia · 2024Article
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Myeloid CCN3 protects against aortic valve calcification.Cell communication and signaling : CCS · 2023Article
- Mechanical injury accentuates lipid deposition in ApoEFrontiers in cardiovascular medicine · 2023Article
- Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart.Cardiovascular research · 2022Article
- Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis.Frontiers in cardiovascular medicine · 2022Article
- 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
- Engineering the aortic valve extracellular matrix through stages of development, aging, and disease.Journal of molecular and cellular cardiology · 2021Review
- Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity.Biomedicines · 2021Article
- Extracellular Matrix in Calcific Aortic Valve Disease: Architecture, Dynamic and Perspectives.International journal of molecular sciences · 2021Review
- Dissecting Calcific Aortic Valve Disease-The Role, Etiology, and Drivers of Valvular Fibrosis.Frontiers in cardiovascular medicine · 2021Review
- Engineered Collagen Matrices.Bioengineering (Basel, Switzerland) · 2020Review
- Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice.Current medical science · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
An insufficient understanding of calcific aortic valve disease (CAVD) pathogenesis remains a major obstacle in developing treatment strategies for this disease. The aim of the present study was to create engineered environments that mimic the earliest known features of CAVD and apply this in vitro platform to decipher relationships relevant to early valve lesion pathobiology. Glycosaminoglycan (GAG) enrichment is a dominant hallmark of early CAVD, but culture of valvular interstitial cells (VICs) in biomaterial environments containing pathological amounts of hyaluronic acid (HA) or chondroitin sulfate (CS) did not directly increase indicators of disease progression such as VIC activation or inflammatory cytokine production. However, HA-enriched matrices increased production of vascular endothelial growth factor (VEGF), while matrices displaying pathological levels of CS were effective at retaining lipoproteins, whose deposition is also found in early CAVD. Retained oxidized low-density lipoprotein (oxLDL), in turn, stimulated myofibroblastic VIC differentiation and secretion of numerous inflammatory cytokines. OxLDL also increased VIC deposition of GAGs, thereby creating a positive feedback loop to further enrich GAG content and promote disease progression. Using this disease-inspired in vitro platform, we were able to model a complex, multistep pathological sequence, with our findings suggesting distinct roles for individual GAGs in outcomes related to valve lesion progression, as well as key differences in cell-lipoprotein interactions compared with atherosclerosis. We propose a pathogenesis cascade that may be relevant to understanding early CAVD and envision the extension of such models to investigate other tissue pathologies or test pharmacological treatments.
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