ArticlePloS one2011
Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 185 citations in OpenAlex.
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- Hypertensive stretch regulates endothelial cell inflammation and apoptosis through ceramide metabolism.American journal of physiology. Cell physiology · 2026Article
- Integrating untargeted metabolomics and machine learning to reveal an aberration of sphingolipid metabolism in cardiometabolic HFpEF.Diabetology & metabolic syndrome · 2026Article
- Review
- T‑cadherin and its impact on human diseases (Review).Molecular medicine reports · 2026Review
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Aromatase Inhibitor Therapy Is Associated with Distinct Plasma Lipidomic Profiles in Postmenopausal Breast Cancer Patients.International journal of molecular sciences · 2026Article
- Sphingolipids in Emotional Well-Being.Journal of neurochemistry · 2026Review
- Serum Lipidomic Profile Signature of Active Acromegaly and Relationships to Cardiovascular Disease.International journal of molecular sciences · 2026Article
- Sex-specific relations of ceramides and white matter hyperintensities in the Rhineland study.Scientific reports · 2025Article
- Plasma metabolites associated with endometriosis in adolescents and young adults.Human reproduction (Oxford, England) · 2025Article
- Characterizing the gut microbiota composition in Taiwanese hypertensive patients using 16S rRNA sequencing analysis.International journal of medical sciences · 2025Article
- Cardiac dysfunction and altered gene expression in acid ceramidase-deficient mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- Coronary heart disease and type 2 diabetes metabolomic signatures in the Middle East.Frontiers in endocrinology · 2025Article
- Increased serum anti-ceramide antibodies and decreased sphingosine-1-phosphate levels in patients with obstructive sleep apnea syndrome as potential markers of endothelial dysfunction.Frontiers in molecular biosciences · 2025Article
- Metabolic Signatures of Blood Pressure and Risk of Cardiovascular Diseases.Journal of the American Heart Association · 2024Article
- Glycosphingolipids in Cardiovascular Disease: Insights from Molecular Mechanisms and Heart Failure Models.Biomolecules · 2024Review
- Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?Nutrients · 2024Review
- Sphingolipids and Chronic Kidney Disease.Journal of clinical medicine · 2024Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. METHODS AND
findingsIn isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p<0.05). Imaging mass spectrometry and immunohistochemistry indicated that these contractions were most likely mediated by ceramide and dependent on iPLA(2), cyclooxygenase-1 and thromboxane synthase. Expression levels of these enzymes were higher in SHR vessels. In concurrence, infusion of dimethylsphingosine caused a marked rise in blood pressure in anesthetized SHR (42±4%; n = 7), but not in WKY (-12±10%; n = 6). Lipidomics analysis by mass spectrometry, revealed elevated levels of ceramide in arterial tissue of SHR compared to WKY (691±42 vs. 419±27 pmol, n = 3-5 respectively, p<0.05). These pronounced alterations in SHR sphingolipid biology are also reflected in increased plasma ceramide levels (513±19 pmol WKY vs. 645±25 pmol SHR, n = 6-12, p<0.05). Interestingly, we observed similar increases in ceramide levels (correlating with hypertension grade) in plasma from humans with essential hypertension (185±8 pmol vs. 252±23 pmol; n = 18 normotensive vs. n = 19 hypertensive patients, p<0.05).
conclusionsHypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone.
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