ArticleCardiovascular research2013
Cathepsin S-mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Suppression of CSF2RA macrophage polarisation impacts pathological cardiac remodelling in mice.Scientific reports · 2026Article
- Cathepsin S: a double-edged protease in barrier damage, neuroimmune inflammation, and tissue repair, with implications for dermatology.Frontiers in immunology · 2026Review
- Exploring the Skin Benefits of Extremophilic Postbiotics fromMicroorganisms · 2025Article
- Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles activate CD4+ T cells from Chagas cardiomyopathy patients and are associated with ventricular dysfunction.Frontiers in immunology · 2025Article
- Cathepsin S: molecular mechanisms in inflammatory and immunological processes.Frontiers in immunology · 2025Review
- Histone deacetylase 6 controls cardiac fibrosis and remodelling through the modulation of TGF-β1/Smad2/3 signalling in post-infarction mice.Journal of cellular and molecular medicine · 2024Article
- Nuclear ATP-citrate lyase regulates chromatin-dependent activation and maintenance of the myofibroblast gene program.Nature cardiovascular research · 2024Article
- The roles of intracellular proteolysis in cardiac ischemia-reperfusion injury.Basic research in cardiology · 2023Review
- Overview of multifunctional cysteinyl cathepsins in atherosclerosis-based cardiovascular disease: from insights into molecular functions to clinical implications.Cell & bioscience · 2023Review
- Article
- Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice.Theranostics · 2023Article
- Multi‑faceted roles of cathepsins in ischemia reperfusion injury (Review).Molecular medicine reports · 2022Review
- Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice.Annals of translational medicine · 2022Article
- The role of CD74 in cardiovascular disease.Frontiers in cardiovascular medicine · 2022Review
- PPARγ activation improves the microenvironment of perivascular adipose tissue and attenuates aortic stiffening in obesity.Journal of biomedical science · 2021Article
- Association of Circulating Cathepsin S and Cardiovascular Disease Among Patients With Type 2 Diabetes: A Cross-Sectional Community-Based Study.Frontiers in endocrinology · 2021Article
- Eosinophils improve cardiac function after myocardial infarction.Nature communications · 2020Article
- Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.Respiratory research · 2020Review
- Cysteinyl cathepsins in cardiovascular diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- Circulating proteomic signature of early death in heart failure patients with reduced ejection fraction.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundExtracellular matrix (ECM) turnover plays an important role in left ventricular (LV) remodelling following myocardial infarction (MI). Cysteinyl cathepsins contribute to ECM catabolism in arterial diseases, suggesting their participation in post-MI remodelling. METHODS AND
resultsLeft anterior descending artery ligation-induced MI in mice showed increased expression and activity of cathepsin S (CatS). Administration of a non-selective cathepsin inhibitor, E64d, aggravated LV dysfunction at 7 and 28 days post-MI. Mechanistic studies showed that E64d increased post-MI inflammatory cell accumulation and cytokine expression, but did not affect apoptosis or angiogenesis in infarcted myocardium. Furthermore, E64d suppressed TGF-β1-induced Smad2 and Smad3 activation and expression of fibronectin extra domain A (ED-A), an alternatively spliced fibronectin variant, and subsequently prevented cardiac fibroblast trans-differentiation into myofibroblast, which contributed to post-MI collagen and fibronectin synthesis and deposition. Consistently, selective inhibition or genetically determined deficiency of CatS also reduced myocardial Smad2 and Smad3 activation and ED-A fibronectin expression, thus suppressing fibroblast trans-differentiation and resulting in adverse collagen turnover and impaired cardiac function-recapitulating the findings in mice treated with E64d.
conclusionAlong with its established activities in ECM degradation, CatS plays novel roles in TGF-β1 signalling, myofibroblast trans-differentiation, and ECM protein synthesis, thereby regulating scar formation in the infarcted myocardium and preserving LV function after experimental MI.
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Registered trials
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.