ArticlePloS one2014
Pentosan polysulfate decreases myocardial expression of the extracellular matrix enzyme ADAMTS4 and improves cardiac function in vivo in rats subjected to pressure overload by aortic banding.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness.Scientific reports · 2018Trial
- ADAM and ADAMTS proteases as integrative hubs in heart failure pathogenesis and therapy.iScience · 2026Review
- The ADAMTS family: from extracellular matrix proteases to orchestrators of fibrosis.Cell communication and signaling : CCS · 2026Review
- The Dual Role of ADAMTS1 in Cardiovascular Remodeling: Balancing Extracellular Matrix Homeostasis and Pathological States.Journal of cardiovascular development and disease · 2025Review
- Matrisome remodeling in the myocardium of hypertrophic cardiomyopathy; novel targets for molecular diagnostics.Frontiers in cell and developmental biology · 2025Review
- Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hitting the Target! Challenges and Opportunities for TGF-β Inhibition for the Treatment of Cardiac fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Temporal expression and spatial distribution of the proteoglycan versican during cardiac fibrosis development.Matrix biology plus · 2023Article
- Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway.bioRxiv : the preprint server for biology · 2023Article
- A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4 Regulates Pulmonary Vascular Hyperpermeability through Destruction of Glycocalyx in Acute Respiratory Distress Syndrome.International journal of molecular sciences · 2023Article
- Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction.Cardiovascular research · 2023Article
- Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Hypochlorous Acid and Chloramines Induce Specific Fragmentation and Cross-Linking of the G1-IGD-G2 Domains of Recombinant Human Aggrecan, and Inhibit ADAMTS1 Activity.Antioxidants (Basel, Switzerland) · 2023Article
- Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation.Frontiers in immunology · 2023Article
- ADAM and ADAMTS disintegrin and metalloproteinases as major factors and molecular targets in vascular malfunction and disease.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Transcriptional, Post-Transcriptional, and Post-Translational Mechanisms Rewrite the Tubulin Code During Cardiac Hypertrophy and Failure.Frontiers in cell and developmental biology · 2022Article
- Cellular Heterogeneity of the Heart.Frontiers in cardiovascular medicine · 2022Review
- The extracellular matrix glycoprotein ADAMTSL2 is increased in heart failure and inhibits TGFβ signalling in cardiac fibroblasts.Scientific reports · 2021Article
- Regulation of ADAMTS Proteases.Frontiers in molecular biosciences · 2021Review
- ADAMTS proteases in cardiovascular physiology and disease.Open biology · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe hypothesized that cleavage of the extracellular matrix (ECM) proteoglycans versican and aggrecan by ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteases, which contributes to stress-induced ECM-reorganization in atherogenesis and osteoarthritis, also play a role in heart failure development.
objectivesThe primary objective was to identify alterations in expression of ADAMTS versicanases and aggrecanases during development of heart failure, while evaluation of the effects of in vivo modulation of relevant changes in ADAMTS activity constituted the secondary objective.
methodsMyocardial levels of versican, aggrecan, and their ADAMTS cleaving proteases were examined in Wistar rats six weeks after aortic banding (AB), and versican and selected ADAMTS versicanases were further analyzed in neonatal cardiomyocytes (NCM) and cardiac fibroblasts (NFB) after stimulation by inflammatory mediators. Based on the initial findings, ADAMTS4 was selected the most promising therapeutic target. Thus, rats with AB were treated with pentosan polysulfate (PPS), a polysaccharide with known ADAMTS4-inhibitory properties, and effects on versican fragmentation, left ventricular function and geometry were evaluated.
resultsWe discovered that myocardial mRNA and protein levels of ADAMTS1 and -4, and mRNA levels of versican, aggrecan, and ADAMTS8 increased after AB, and TNF-α and IL-1β synergistically increased mRNA of versican and ADAMTS4 in NCM and NFB and secretion of ADAMTS4 from NCM. Furthermore, PPS-treatment improved systolic function, demonstrated by an improved fractional shortening (vehicle 48±3% versus PPS 60±1%, p<0.01) after AB. Following PPS-treatment, we observed an ∼80% reduction in myocardial ADAMTS4 mRNA (p = 0.03), and ∼50% reduction in the extracellular amount of the p150 versican fragments (p = 0.05), suggesting reduced versicanase activity.
conclusionsOur findings suggest that AB induces an increase in myocardial ADAMTS4 versicanase activity, and that PPS-treatment improved systolic function in the pressure-overloaded heart, holding promise as a novel therapeutic agent in heart failure.
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