ArticleThe Journal of biological chemistry2012
Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 168 citations in OpenAlex.
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- Circulating sphingosine-1-phosphate depletion is associated with endothelial activation and altered brain-endothelial S1P pathway expression in ischemic stroke.Fluids and barriers of the CNS · 2026Article
- Body roundness index mediates the association between high-density lipoprotein cholesterol and diabetic retinopathy: a population-based cross-sectional study.BMC endocrine disorders · 2026Article
- Apolipoprotein M: Structural insights, functional roles, and therapeutic approaches in vascular disease.The Journal of biological chemistry · 2026Review
- The potential effect of albumin replacement on immune modulation and sphingosine 1-phosphate dynamics.Scientific reports · 2026Observational
- Ceramide-based machine learning models for the diagnosis of unstable angina: a prospective multicenter study.European journal of medical research · 2026Article
- HDL in Abdominal Aortic Aneurysm: Mechanistic Insight and Therapeutic Potential.Current atherosclerosis reports · 2026Review
- HDL protein composition differs between young white European and South Asian men before and after weight gain.Clinical science (London, England : 1979) · 2025Article
- Beyond High-density Lipoprotein-cholesterol: Unraveling the Complexity of High-density Lipoprotein Functionality.Journal of atherosclerosis and thrombosis · 2025Review
- ApoM and Major Adverse Cardiovascular Events in Chronic Kidney Disease: A Prospective Cohort Study.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Unraveling sphingolipid dynamics in late-onset preeclampsia: insights from lipidomic analysis.Biochemia medica · 2025Article
- Ying and Yang of Ceramide in the Vascular Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Endothelial cell sphingosine 1-phosphate receptor 1 restrains VE-cadherin cleavage and attenuates experimental inflammatory arthritis.JCI insight · 2024Article
- The effect of normobaric hypoxia on acute exercise-induced changes in blood sphingoid base-1-phosphates metabolism in cyclists.Biology of sport · 2024Article
- Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Entering, Linked with the Sphinx: Lysophosphatidic Acids Everywhere, All at Once, in the Oral System and Cancer.International journal of molecular sciences · 2023Review
- Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific Evidence.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function.
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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.