ArticleCirculation2009
Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 304 citations in OpenAlex.
- Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies.Clinical interventions in aging · 2017Pooled it
- Prognostic effect of high-flux hemodialysis in patients with chronic kidney disease.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2016Pooled it
- QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The Framingham Study.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Trial
- Progress on the related mechanisms of vascular calcification in autogenous arteriovenous fistula in hemodialysis patients.Renal failure · 2026Review
- Review
- Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- An interpretable machine learning model for predicting 1-year major adverse cardiovascular events in patients with type 2 diabetes and hypertension.Frontiers in medicine · 2026Article
- Phthalate exposure is associated with increased CVD risk in CKD: evidence from NHANES and network toxicology analysis.Renal failure · 2025Article
- Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies.Biomedicines · 2025Review
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation.Frontiers in cardiovascular medicine · 2025Review
- Calcification of the elastic component: the impact on the cardiovascular system.Frontiers in cardiovascular medicine · 2025Review
- Imaging antigen processing and presentation in cancer.Immunotherapy advances · 2025Review
- Macrophages in Calcific Aortic Valve Disease: Paracrine and Juxtacrine Disease Drivers.Biomolecules · 2024Review
- FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.Redox biology · 2024Article
- The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics.Basic research in cardiology · 2024Review
- Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult.Nature cardiovascular research · 2024Article
- Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays.Science advances · 2024Article
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic rats.Frontiers in nephrology · 2024Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundClinical studies have demonstrated that 50% of individuals with chronic renal disease (CRD) die of cardiovascular causes, including advanced calcific arterial and valvular disease; however, the mechanisms of accelerated calcification in CRD remain obscure, and no therapies can prevent disease progression. We recently demonstrated in vivo that inflammation triggers cardiovascular calcification. In vitro evidence also indicates that elastin degradation products may promote osteogenesis. Here, we used genetically modified mice and molecular imaging to test the hypothesis in vivo that cathepsin S (catS), a potent elastolytic proteinase, accelerates calcification in atherosclerotic mice with CRD induced by 5/6 nephrectomy. METHODS AND
resultsApolipoprotein-deficient (apoE(-/-))/catS(+/+) (n=24) and apoE(-/-)/catS(-/-) (n=24) mice were assigned to CRD and control groups. CRD mice had significantly higher serum phosphate, creatinine, and cystatin C levels than those without CRD. To visualize catS activity and osteogenesis in vivo, we coadministered catS-activatable and calcification-targeted molecular imaging agents 10 weeks after nephrectomy. Imaging coregistered increased catS and osteogenic activities in the CRD apoE(-/-)/catS(+/+) cohort, whereas CRD apoE(-/-)/catS(-/-) mice exhibited less calcification. Quantitative histology demonstrated greater catS-associated elastin fragmentation and calcification in CRD apoE(-/-)/catS(+/+) than CRD apoE(-/-)/catS(-/-) aortas and aortic valves. Notably, catS deletion did not cause compensatory increases in RNA levels of other elastolytic cathepsins or matrix metalloproteinases. Elastin peptide and recombinant catS significantly increased calcification in smooth muscle cells in vitro, a process further amplified in phosphate-enriched culture medium.
conclusionsThe present study provides direct in vivo evidence that catS-induced elastolysis accelerates arterial and aortic valve calcification in CRD, providing new insight into the pathophysiology of cardiovascular calcification.
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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.