ArticleScientific reports2018
Identification of DKK-1 as a novel mediator of statin effects in human endothelial cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Lipid Metabolism as a Therapeutic Target in Arrhythmogenic Cardiomyopathy: Emerging Therapeutic Implications of Lipid-Lowering Therapy.Reviews in cardiovascular medicine · 2026Review
- Prenylcysteine Oxidase 1 Deficiency Protects the Cardiac Muscle Cell Line HL-1 Against Ischaemic/Hypoxic Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- HuR-Regulated Extracellular Vesicles Promote Endothelial Cell Remodeling in Pancreatic Cancer.Cancer research communications · 2025Article
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease.JVS-vascular science · 2025Review
- Statin effect on arrhythmogenic cardiomyopathy disease progression (SEARCH): Randomized clinical study protocol.PloS one · 2025Article
- Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.Medicina (Kaunas, Lithuania) · 2024Article
- Multiplexed MRM-based proteomics for identification of circulating proteins as biomarkers of cardiovascular damage progression associated with diabetes mellitus.Cardiovascular diabetology · 2024Article
- Endothelial Dickkopf-1 Promotes Smooth Muscle Cell-derived Foam Cell Formation via USP53-mediated Deubiquitination of SR-A During Atherosclerosis.International journal of biological sciences · 2024Article
- Proteome Profiling of the Dura Mater in Patients with Moyamoya Angiopathy.International journal of molecular sciences · 2023Article
- Prenylcysteine Oxidase 1 Is a Key Regulator of Adipogenesis.Antioxidants (Basel, Switzerland) · 2023Article
- Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges.International journal of molecular sciences · 2023Review
- The Effects of Silencing PTX3 on the Proteome of Human Endothelial Cells.International journal of molecular sciences · 2022Article
- RNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease.Journal of the American Heart Association · 2022Article
- Simvastatin rescues memory and granule cell maturation through the Wnt/β-catenin signaling pathway in a mouse model of Alzheimer's disease.Cell death & disease · 2022Article
- Inhibition of CXXC5 function reverses obesity-related metabolic diseases.Clinical and translational medicine · 2022Article
- Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery.Geburtshilfe und Frauenheilkunde · 2021Article
- Prenylcysteine oxidase 1, an emerging player in atherosclerosis.Communications biology · 2021Article
- Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy.EMBO molecular medicine · 2021Article
- CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
This study shows that DKK-1, a member of the Dickkopf family and a regulator of the Wnt pathways, represents a novel target of statins which, through the inhibition of HMG-CoA reductase and of non-steroidal isoprenoid intermediates, exert extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. We found that atorvastatin downregulates DKK-1 protein (-88.3 ± 4.1%) and mRNA expression (-90 ± 4.2%) through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. Further, a combined approach based on the integration of label-free quantitative mass spectrometry based-proteomics and gene silencing allowed us to demonstrate that DKK-1 itself mediates, at least in part, statin effects on human endothelial cells. Indeed, DKK-1 is responsible for the regulation of the 21% of the statin-modulated proteins, which include, among others, clusterin/apoJ, plasminogen activator inhibitor type 1 (PAI-1), myristoylated alanine-rich C-kinase substrate (MARCKS), and pentraxin 3 (PTX3). The Gene Ontology enrichment annotation revealed that DKK-1 is also a potential mediator of the extracellular matrix organization, platelet activation and response to wounding processes induced by statin. Finally, we found that plasma level of DKK-1 from cholesterol-fed rabbits treated with atorvastatin (2.5 mg/kg/day for 8 weeks) was lower (-42 ± 23%) than that of control animals. Thus, DKK-1 is not only a target of statin but it directly regulates the expression of molecules involved in a plethora of biological functions, thus expanding its role, which has been so far restricted mainly to cancer.
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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 Socratic graph.