ArticleOncotarget2017
Nε-carboxymethyl-lysine promotes calcium deposition in VSMCs via intracellular oxidative stress-induced PDK4 activation and alters glucose metabolism.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure.Biomedicines · 2025Review
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
- Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles Induced by Advanced Glycation End Products on Energy Metabolism in Vascular Endothelial Cells.Kidney international reports · 2025Article
- The Role of Mitochondrial Dysfunction in CKD-Related Vascular Calcification: From Mechanisms to Therapeutics.Kidney international reports · 2024Review
- Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients.Journal of nephrology · 2022Review
- Rye Bread Crust as an Inducer of Antioxidant Genes and Suppressor of NF-κB Pathway In Vivo.Nutrients · 2022Article
- Phenotypic plasticity of vascular smooth muscle cells in vascular calcification: Role of mitochondria.Frontiers in cardiovascular medicine · 2022Review
- Insights Into the Role of Mitochondria in Vascular Calcification.Frontiers in cardiovascular medicine · 2022Review
- Diabetic nephropathy patients show hyper-responsiveness to N6-carboxymethyllysine.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Observational
- Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis.Frontiers in endocrinology · 2022Review
- Mitochondria Homeostasis and Vascular Medial Calcification.Calcified tissue international · 2021Review
- microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4.Cancer gene therapy · 2021Article
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- Article
- Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification.Molecular and cellular biochemistry · 2020Article
- Nϵ-Carboxymethyl-Lysine Deteriorates Vascular Calcification in Diabetic Atherosclerosis Induced by Vascular Smooth Muscle Cell-Derived Foam Cells.Frontiers in pharmacology · 2020Article
- The Role of Nonenzymatic Post-translational Protein Modifications in Uremic Vascular Calcification.Advances in chronic kidney disease · 2019Review
- Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes.Oxidative medicine and cellular longevity · 2019Review
- Advanced glycation end products accelerate calcification in VSMCs through HIF-1α/PDK4 activation and suppress glucose metabolism.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes and vascular calcification are intrinsically linked. We previously reported that advanced glycation end products (AGEs) accelerate calcium deposition in vascular smooth muscle cells (VSMCs) via excessive oxidative stress. However, the underlying mechanism remains poorly understood. Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy metabolism. Since hyperactivation of PDK4 has been reported in calcified vessels and in patients with diabetes mellitus, inhibition of PDK4 expression may be a strategy for the prevention of diabetic vascular calcification. In this study, we used a rat VSMC model to investigate the role of PDK4 in diabetic vascular calcification and further explore the underlying mechanisms. We observed that Nε-carboxymethyl-lysine (CML), which is a major immunogen of AGEs, accelerated calcium deposition in VSMCs through PDK4 activation. An elevated level of reactive oxygen species (ROS) acted as a signal transduction intermediate to increase PDK4 expression. Either inhibition of PDK4 expression or RAGE (receptor for AGEs) blockade attenuated CML-induced VSMC calcification, as shown by decreased alkaline phosphatase (ALP) activity and runt-related transcription factor 2 (RUNX2) expression. Glucose consumption and lactate production were increased during CML-induced VSMC calcification. Importantly, CML accelerates glycolysis in VSMCs via a PDK4-dependent pathway. In conclusion, this study demonstrates a novel mechanism by which CML promotes VSMC calcification via PDK4 activation and alters glucose metabolism in VSMCs.
Indexed as
Identifiers
What OpenQuestion holds
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.