ArticleCirculation research2024
Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis.
Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis 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.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Novel Quality Metrics for Assessing the Reproducibility and Translational Relevance of Mouse Transverse Aortic Constriction Experiments: A Systematic Review.Journal of the American Heart Association · 2026Pooled it
- A multi-metabolite signature robustly predicts long-term mortality in the PREDIMED trial and several US cohorts.Metabolism: clinical and experimental · 2025Trial
- Sphingomyelin as a key negative mediator in atrial fibrillation via lipid profiling analysis and functional identification.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Lipid metabolism in moyamoya disease: Emerging evidence, vascular remodeling, and therapeutic implications.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- The Sphingolipid Balance and Endothelial Dysfunction in Lysosomal Storage Diseases: Shared Mechanisms in Gaucher, Niemann-Pick and Fabry Disease.International journal of molecular sciences · 2026Review
- Plasma Metabolomics of Thrombectomy-Treated Patients Highlights Metabolic Pathways Underlying Disease and Recovery.CNS neuroscience & therapeutics · 2026Article
- Deep chemical structure graph learning deciphers the lipotoxicity code of hypertriglyceridemic pancreatitis.NPJ digital medicine · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Beyond the Apnea-Hypopnea Index: Circulating Biomarkers and Device-Based Metrics for Cardiometabolic Risk Stratification in Obstructive Sleep Apnea.Journal of clinical medicine · 2026Review
- The expanding role of Nogo-B in hypertension: linking kidney physiology, endothelial function and inflammation.Journal of hypertension · 2026Review
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Metabolomic Biomarkers for Non-Invasive Diagnosis of Coronary Artery Disease and Obstructive Sleep Apnea Co-Occurrence.Nature and science of sleep · 2026Article
- Article
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets.Cardiovascular research · 2025Review
- Review
- Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases.Nature communications · 2025Article
- Dysregulated cellular metabolism drives atherosclerotic plaque progression: a multi-cellular perspective.Frontiers in cardiovascular medicine · 2025Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 5 countries.
Funding
Abstract
backgroundGrowing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood.
methodsWe used an established model of coronary atherosclerosis in mice, combined with sphingolipidomics, RNA-sequencing, flow cytometry, and immunostaining to investigate the contribution of sphingolipid metabolism and signaling to endothelial cell (EC) activation and dysfunction.
resultsWe demonstrated that hemodynamic stress induced an early metabolic rewiring towards endothelial sphingolipid de novo biosynthesis, favoring S1P signaling over ceramides as a protective response. This finding is a paradigm shift from the current belief that ceramide accrual contributes to endothelial dysfunction. The enzyme SPT (serine palmitoyltransferase) commences de novo biosynthesis of sphingolipids and is inhibited by NOGO-B (reticulon-4B), an ER membrane protein. Here, we showed that NOGO-B is upregulated by hemodynamic stress in myocardial EC of ApoE
conclusionsThese data demonstrated that hemodynamic stress induced a protective rewiring of sphingolipid metabolism, favoring S1P over ceramide. NOGO-B deletion sustained the rewiring of sphingolipid metabolism toward S1P protecting EC from activation under hemodynamic stress and refraining coronary atherosclerosis. These findings also set forth the foundation for sphingolipid-based therapeutics to limit atheroprogression.
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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.