ArticleDevelopmental biology2011
Altered versican cleavage in ADAMTS5 deficient mice; a novel etiology of myxomatous valve disease.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 123 citations in OpenAlex.
- Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice.Disease models & mechanisms · 2026Article
- An Overview of ADAMTS Proteases.Methods in molecular biology (Clifton, N.J.) · 2026Review
- ADAMTS5 Orchestrates Cell Lineage Specific Patterning and Extracellular Matrix Organization During Semilunar Valve Development.Journal of cardiovascular development and disease · 2025Article
- Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets.Genome research · 2024Article
- Gastruloids are competent to specify both cardiac and skeletal muscle lineages.Nature communications · 2024Article
- Combined genetic-pharmacologic inactivation of tightly linked ADAMTS proteases in temporally specific windows uncovers distinct roles for versican proteolysis and glypican-6 in cardiac development.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Molecular Pathways and Animal Models of Semilunar Valve and Aortic Arch Anomalies.Advances in experimental medicine and biology · 2024Review
- ADAMTS Proteases: Their Multifaceted Role in the Regulation of Cancer Metastasis.Diseases & research · 2024Article
- Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway.Neural regeneration research · 2024Article
- PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.Circulation research · 2023Article
- Temporal Progression of Aortic Valve Pathogenesis in a Mouse Model of Osteogenesis Imperfecta.Journal of cardiovascular development and disease · 2023Article
- Increased Proteoglycanases in Pulmonary Valves after Birth Correlate with Extracellular Matrix Maturation and Valve Sculpting.Journal of cardiovascular development and disease · 2023Article
- Extracellular Matrix Profiling and Disease Modelling in Engineered Vascular Smooth Muscle Cell Tissues.Matrix biology plus · 2022Article
- Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Journal of clinical medicine · 2022Review
- Isolation and Purification of Versican and Analysis of Versican Proteolysis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Identification of novel ADAMTS1, ADAMTS4 and ADAMTS5 cleavage sites in versican using a label-free quantitative proteomics approach.Journal of proteomics · 2021Article
- Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.Journal of cardiovascular development and disease · 2021Review
- Article
- A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the GluMatrix biology plus · 2021Article
- Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.Journal of molecular and cellular cardiology · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
In fetal valve maturation the mechanisms by which the relatively homogeneous proteoglycan-rich extracellular matrix (ECM) of endocardial cushions is replaced by a specialized and stratified ECM found in mature valves are not understood. Therefore, we reasoned that uncovering proteases critical for 'remodeling' the proteoglycan rich (extracellular matrix) ECM may elucidate novel mechanisms of valve development. We have determined that mice deficient in ADAMTS5, (A Disintegrin-like And Metalloprotease domain with ThromboSpondin-type 1 motifs) which we demonstrated is expressed predominantly by valvular endocardium during cardiac valve maturation, exhibited enlarged valves. ADAMTS5 deficient valves displayed a reduction in cleavage of its substrate versican, a critical cardiac proteoglycan. In vivo reduction of versican, in Adamts5(-/-) mice, achieved through Vcan heterozygosity, substantially rescued the valve anomalies. An increase in BMP2 immunolocalization, Sox9 expression and mesenchymal cell proliferation were observed in Adamts5(-/-) valve mesenchyme and correlated with expansion of the spongiosa (proteoglycan-rich) region in Adamts5(-/-) valve cusps. Furthermore, these data suggest that ECM remodeling via ADAMTS5 is required for endocardial to mesenchymal signaling in late fetal valve development. Although adult Adamts5(-/-) mice are viable they do not recover from developmental valve anomalies and have myxomatous cardiac valves with 100% penetrance. Since the accumulation of proteoglycans is a hallmark of myxomatous valve disease, based on these data we hypothesize that a lack of versican cleavage during fetal valve development may be a potential etiology of adult myxomatous valve disease.
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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.