ArticleCardiovascular research2023
Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- ADAMTS4 mediates LPS-induced cardiac injury and myocardial fibrosis through proteolytic cleavage of TSP1.Clinical and translational medicine · 2026Article
- ADAM and ADAMTS proteases as integrative hubs in heart failure pathogenesis and therapy.iScience · 2026Review
- An integrated cell atlas of 2.4 million cardiac cells across 209 individuals in health and disease.Nature cardiovascular research · 2026Article
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Direct Extracellular Matrix Modulation Attenuates Intestinal Fibrosis via a Fibronectin-Targeted Approach.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The ADAMTS family: from extracellular matrix proteases to orchestrators of fibrosis.Cell communication and signaling : CCS · 2026Review
- TGF-β in chronic kidney disease: a controversy for decades.Frontiers in immunology · 2026Review
- High Burden of Premature Ventricular Contractions Upregulates Transcriptional Markers of Inflammation and Promotes Adverse Cardiac Remodeling Linked to Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- ADAM8 deficiency in macrophages promotes cardiac repair after myocardial infarction via ANXA2-mTOR-autophagy pathway.Journal of advanced research · 2025Article
- The secreted protease ADAMTS18 is a novel activator of latent TGF-β to exacerbate renal fibrosis.Communications biology · 2025Article
- ADAMTS4 Reduction Contributes to Extracellular Matrix Deposition and Impaired Myogenesis in the Skeletal Muscle of Cigarette Smoke-Exposed Mice.Biomedicines · 2025Article
- Non-invasive estimation of left ventricular chamber stiffness using cardiovascular magnetic resonance and echocardiography.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2025Article
- Article
- ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.Communications biology · 2024Article
- Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment.Reviews in cardiovascular medicine · 2024Review
- Hitting the Target! Challenges and Opportunities for TGF-β Inhibition for the Treatment of Cardiac fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment.Molecular biology reports · 2024Review
- Temporal expression and spatial distribution of the proteoglycan versican during cardiac fibrosis development.Matrix biology plus · 2023Article
- Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHeart failure is a condition with high mortality rates, and there is a lack of therapies that directly target maladaptive changes in the extracellular matrix (ECM), such as fibrosis. We investigated whether the ECM enzyme known as A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) 4 might serve as a therapeutic target in treatment of heart failure and cardiac fibrosis. METHODS AND
resultsThe effects of pharmacological ADAMTS4 inhibition on cardiac function and fibrosis were examined in rats exposed to cardiac pressure overload. Disease mechanisms affected by the treatment were identified based on changes in the myocardial transcriptome. Following aortic banding, rats receiving an ADAMTS inhibitor, with high inhibitory capacity for ADAMTS4, showed substantially better cardiac function than vehicle-treated rats, including ∼30% reduction in E/e' and left atrial diameter, indicating an improvement in diastolic function. ADAMTS inhibition also resulted in a marked reduction in myocardial collagen content and a down-regulation of transforming growth factor (TGF)-β target genes. The mechanism for the beneficial effects of ADAMTS inhibition was further studied in cultured human cardiac fibroblasts producing mature ECM. ADAMTS4 caused a 50% increase in the TGF-β levels in the medium. Simultaneously, ADAMTS4 elicited a not previously known cleavage of TGF-β-binding proteins, i.e. latent-binding protein of TGF-β and extra domain A-fibronectin. These effects were abolished by the ADAMTS inhibitor. In failing human hearts, we observed a marked increase in ADAMTS4 expression and cleavage activity.
conclusionInhibition of ADAMTS4 improves cardiac function and reduces collagen accumulation in rats with cardiac pressure overload, possibly through a not previously known cleavage of molecules that control TGF-β availability. Targeting ADAMTS4 may serve as a novel strategy in heart failure treatment, in particular, in heart failure with fibrosis and diastolic dysfunction.
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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.