ArticlePloS one2013
Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification via p38 mitogen-activated protein kinase signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Sphingolipid Metabolism: A Pathological Hub Linking Lipid Dysregulation and Chronic Inflammation in Atherosclerotic Cardiovascular Disease.Journal of inflammation research · 2026Review
- Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease.Journal of cellular physiology · 2026Article
- Mechanistic insights into lipoprotein(a)-induced cardiomyocyte ferroptosis via ROS/p38/p53 signaling.Frontiers in medicine · 2026Article
- Heterogeneity of common carotid artery and abdominal aorta: an angle of sphingolipid metabolism in vascular smooth muscle cells.Biomedical engineering online · 2025Article
- Impact of Lipid Oxidation Products on Inflammation and Insulin Resistance: A Focus on Mechanisms of Action.Cell biochemistry and biophysics · 2025Review
- A Transcriptomic Approach to Sex Differences in Calcific Aortic Valve Stenosis in Patients with a Tricuspid Aortic Valve.CJC open · 2025Article
- Metabolic dysfunction-associated steatotic liver disease (MASLD) biomarkers and progression of lower limb arterial calcification in patients with type 2 diabetes: a prospective cohort study.Cardiovascular diabetology · 2025Observational
- Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.Aging · 2025Article
- Article
- Resveratrol ameliorates osteogenic differentiation, calcification, and apoptosis of VSMCs through regulating JNK/Bax signaling.Frontiers in pharmacology · 2025Article
- Emerging role of sphingolipids and extracellular vesicles in development and therapeutics of cardiovascular diseases.International journal of cardiology. Heart & vasculature · 2024Review
- Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate.Antioxidants (Basel, Switzerland) · 2023Review
- The therapeutic potential of sphingolipids for cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Mitophagy in atherosclerosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- New insight into dyslipidemia-induced cellular senescence in atherosclerosis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model.Cells · 2022Article
- Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification.International journal of molecular sciences · 2022Review
- The Role of Obesity, Inflammation and Sphingolipids in the Development of an Abdominal Aortic Aneurysm.Nutrients · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification is associated with significant cardiovascular morbidity and mortality, and has been demonstrated as an actively regulated process resembling bone formation. Oxidized low density lipoprotein (Ox-LDL) has been identified as a regulatory factor involved in calcification of vascular smooth muscle cells (VSMCs). Additionally, over-expression of recombinant human neutral sphingomyelinase (N-SMase) has been shown to stimulate VSMC apoptosis, which plays an important role in the progression of vascular calcification. The aim of this study is to investigate whether ceramide regulates Ox-LDL-induced calcification of VSMCs via activation of p38 mitogen-activated protein kinase (MAPK) pathway. Ox-LDL increased the activity of N-SMase and the level of ceramide in cultured VSMCs. Calcification and the osteogenic transcription factor, Msx2 mRNA expression were reduced by N-SMase inhibitor, GW4869 in the presence of Ox-LDL. Usage of GW4869 inhibited Ox-LDL-induced apoptosis in VSMCs, an effect which was reversed by C2-ceramide. Additionally, C2-ceramide treatment accelerated VSMC calcification, with a concomitant increase in ALP activity. Furthermore, C2-ceramide treatment enhanced Ox-LDL-induced VSMC calcification. Addition of caspase inhibitor, ZVAD-fmk attenuated Ox-LDL-induced calcification. Both Ox-LDL and C2-ceramide treatment increased the phosphorylation of p38 MAPK. Inhibition of p38 MAPK by SB203580 attenuated Ox-LDL-induced calcification of VSMCs. These data suggest that Ox-LDL activates N-SMase-ceramide signaling pathway, and stimulates phosphorylation of p38 MAPK, leading to apoptosis in VSMCs, which initiates VSMC calcification.
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