ArticleDiabetes2015
Ceramide-Initiated Protein Phosphatase 2A Activation Contributes to Arterial Dysfunction In Vivo.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Blood metabolome of cardiovascular disease, diabetic kidney disease, and diabetic retinopathy in type 2 diabetes patients: A systematic review and meta-analysis.Endocrine research · 2025Pooled it
- Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease.The Journal of clinical investigation · 2020Trial
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Hypertensive stretch regulates endothelial cell inflammation and apoptosis through ceramide metabolism.American journal of physiology. Cell physiology · 2026Article
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Lipid Peroxidation in Cancer Therapy: Molecular Mechanisms Involving Oxidative Stress, Cell Death, and Therapeutic Response.Molecules (Basel, Switzerland) · 2026Review
- Bryostatin-1 improves function in arteries with suppressed endothelial cell autophagy.GeroScience · 2026Article
- Impact of C-Terminal PKC Phosphorylation on TRPC6 Current Kinetics.International journal of molecular sciences · 2025Article
- Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025Review
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- Ceramide in Coronary Artery Disease: Troublesome or Helpful Future Tools in the Assessment of Risk Prediction and Therapy Effectiveness?Metabolites · 2025Review
- Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases.Nature communications · 2025Article
- Machine Learning based Model Reveals the Metabolites Involved in Coronary Artery Disease.Biomedical engineering and computational biology · 2025Article
- Differential effects of PCSK9 inhibitors and statins on plasma ceramides in coronary artery disease.Frontiers in pharmacology · 2025Article
- The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease.Lipids in health and disease · 2024Article
- Biomarkers and Target-Specific Small-Molecule Drugs in Alzheimer's Diagnostic and Therapeutic Research: From Amyloidosis to Tauopathy.Neurochemical research · 2024Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Hypersensitive blood vessels in Clarkson disease.The Journal of clinical investigation · 2024Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex.Advanced biology · 2024Article
20 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
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Prior studies have implicated accumulation of ceramide in blood vessels as a basis for vascular dysfunction in diet-induced obesity via a mechanism involving type 2 protein phosphatase (PP2A) dephosphorylation of endothelial nitric oxide synthase (eNOS). The current study sought to elucidate the mechanisms linking ceramide accumulation with PP2A activation and determine whether pharmacological inhibition of PP2A in vivo normalizes obesity-associated vascular dysfunction and limits the severity of hypertension. We show in endothelial cells that ceramide associates with the inhibitor 2 of PP2A (I2PP2A) in the cytosol, which disrupts the association of I2PP2A with PP2A leading to its translocation to the plasma membrane. The increased association between PP2A and eNOS at the plasma membrane promotes dissociation of an Akt-Hsp90-eNOS complex that is required for eNOS phosphorylation and activation. A novel small-molecule inhibitor of PP2A attenuated PP2A activation, prevented disruption of the Akt-Hsp90-eNOS complex in the vasculature, preserved arterial function, and maintained normal blood pressure in obese mice. These findings reveal a novel mechanism whereby ceramide initiates PP2A colocalization with eNOS and demonstrate that PP2A activation precipitates vascular dysfunction in diet-induced obesity. Therapeutic strategies targeted to reducing PP2A activation might be beneficial in attenuating vascular complications that exist in the context of type 2 diabetes, obesity, and conditions associated with insulin resistance.
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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.