ArticleScientific reports2016
Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.British journal of clinical pharmacology · 2021Trial
- Article
- Pamoic acid and carbenoxolone specifically inhibit CRISPR/Cas9 in bacteria, mammalian cells, and mice in a DNA topology-specific manner.Genome biology · 2025Article
- Targeting sepsis through inflammation and oxidative metabolism.World journal of critical care medicine · 2025Review
- Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.International journal of molecular sciences · 2024Article
- The effect of normobaric hypoxia on acute exercise-induced changes in blood sphingoid base-1-phosphates metabolism in cyclists.Biology of sport · 2024Article
- Role of sphingosine 1-phosphate (S1P) in sepsis-associated intestinal injury.Frontiers in medicine · 2023Review
- Editorial: Sphingolipids in cardiovascular diseases: from pathogenesis to therapeutics.Frontiers in cardiovascular medicine · 2023Article
- Stressing the Endothelium to Assess Localized Inflammatory Potential and the Risk for Atherosclerotic Cardiovascular Disease.Circulation · 2021Article
- Deletion or inhibition of SphK1 mitigates fulminant hepatic failure by suppressing TNFα-dependent inflammation and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Dynamics of Vascular Protective and Immune Supportive Sphingosine-1-Phosphate During Cardiac Surgery.Frontiers in immunology · 2021Observational
- Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.International journal of molecular sciences · 2020Review
- Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction.International journal of molecular sciences · 2020Article
- Ribonuclease 1 attenuates septic cardiomyopathy and cardiac apoptosis in a murine model of polymicrobial sepsis.JCI insight · 2020Article
- Article
- S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis.Shock (Augusta, Ga.) · 2020Article
- Ticagrelor Conditioning Effects Are Not Additive to Cardioprotection Induced by Direct NLRP3 Inflammasome Inhibition: Role of RISK, NLRP3, and Redox Cascades.Oxidative medicine and cellular longevity · 2020Article
- The glycocalyx: a novel diagnostic and therapeutic target in sepsis.Critical care (London, England) · 2019Review
- Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities.Frontiers in pediatrics · 2019Review
- Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL).Journal of intensive care · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serum levels of the lipid mediator sphingosine-1-phosphate (S1P) are reduced in septic patients and are inversely associated with disease severity. We show that serum S1P is reduced in human sepsis and in murine models of sepsis. We then investigated whether pharmacological or genetic approaches that alter serum S1P may attenuate cardiac dysfunction and whether S1P signaling might serve as a novel theragnostic tool in sepsis. Mice were challenged with lipopolysaccharide and peptidoglycan (LPS/PepG). LPS/PepG resulted in an impaired systolic contractility and reduced serum S1P. Administration of the immunomodulator FTY720 increased serum S1P, improved impaired systolic contractility and activated the phosphoinositide 3-kinase (PI3K)-pathway in the heart. Cardioprotective effects of FTY720 were abolished following administration of a S1P receptor 2 (S1P2) antagonist or a PI3K inhibitor. Sphingosine kinase-2 deficient mice had higher endogenous S1P levels and the LPS/PepG-induced impaired systolic contractility was attenuated in comparison with wild-type mice. Cardioprotective effects of FTY720 were confirmed in polymicrobial sepsis. We show here for the first time that the impaired left ventricular systolic contractility in experimental sepsis is attenuated by FTY720. Mechanistically, our results indicate that activation of S1P2 by increased serum S1P and the subsequent activation of the PI3K-Akt survival pathway significantly contributes to the observed cardioprotective effect of FTY720.
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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.