ArticleJournal of the American Heart Association2016
Sphingosine-1-Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca2+ Sensitivity and Na+/H+ Exchange and Mediates Protection by Ischemic Preconditioning.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Associations of sphingosine-1-phosphate with thyroid function and structure: a cross-sectional population-based study.European thyroid journal · 2026Article
- S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.Science advances · 2026Article
- PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.Molecular imaging and biology · 2025Article
- The spleen in ischaemic heart disease.Nature reviews. Cardiology · 2025Review
- The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.Epilepsia open · 2025Review
- Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.Theranostics · 2025Article
- Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.Drugs · 2024Review
- Deficiency of the sphingosine-1-phosphate (S1P) transporter Mfsd2b protects the heart against hypertension-induced cardiac remodeling by suppressing the L-type-CaBasic research in cardiology · 2024Article
- Ischemic cardiac stromal fibroblast-derived protein mediators in the infarcted myocardium and transcriptomic profiling at single cell resolution.Functional & integrative genomics · 2024Article
- Sphingolipids: drivers of cardiac fibrosis and atrial fibrillation.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Empagliflozin Ameliorates Ouabain-Induced NaCardiovascular drugs and therapy · 2023Article
- Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases.Biomolecules · 2023Review
- Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction.Nature communications · 2023Article
- Sphingosine-1-phosphate improves outcome of no-reflow acute myocardial infarction via sphingosine-1-phosphate receptor 1.ESC heart failure · 2023Article
- Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.Pharmacological reviews · 2023Review
- Sphingolipid Metabolism and Signaling in Endothelial Cell Functions.Advances in experimental medicine and biology · 2022Review
- The relationship between the number of stenotic coronary arteries and the gut microbiome in coronary heart disease patients.Frontiers in cellular and infection microbiology · 2022Article
- Plasma Exosomal S1PR5 and CARNS1 as Potential Non-invasive Screening Biomarkers of Coronary Heart Disease.Frontiers in cardiovascular medicine · 2022Article
- Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts.American journal of physiology. Heart and circulatory physiology · 2021Article
- Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine-1-Phosphate.Journal of the American Heart Association · 2021Article
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSphingosine-1-phosphate plays vital roles in cardiomyocyte physiology, myocardial ischemia-reperfusion injury, and ischemic preconditioning. The function of the cardiomyocyte sphingosine-1-phosphate receptor 1 (S1P1) in vivo is unknown. METHODS AND
resultsCardiomyocyte-restricted deletion of S1P1 in mice (S1P1 (α) (MHCC) (re)) resulted in progressive cardiomyopathy, compromised response to dobutamine, and premature death. Isolated cardiomyocytes from S1P1 (α) (MHCC) (re) mice revealed reduced diastolic and systolic Ca(2+) concentrations that were secondary to reduced intracellular Na(+) and caused by suppressed activity of the sarcolemmal Na(+)/H(+) exchanger NHE-1 in the absence of S1P1. This scenario was successfully reproduced in wild-type cardiomyocytes by pharmacological inhibition of S1P1 or sphingosine kinases. Furthermore, Sarcomere shortening of S1P1 (α) (MHCC) (re) cardiomyocytes was intact, but sarcomere relaxation was attenuated and Ca(2+) sensitivity increased, respectively. This went along with reduced phosphorylation of regulatory myofilament proteins such as myosin light chain 2, myosin-binding protein C, and troponin I. In addition, S1P1 mediated the inhibitory effect of exogenous sphingosine-1-phosphate on β-adrenergic-induced cardiomyocyte contractility by inhibiting the adenylate cyclase. Furthermore, ischemic precondtioning was abolished in S1P1 (α) (MHCC) (re) mice and was accompanied by defective Akt activation during preconditioning.
conclusionsTonic S1P1 signaling by endogenous sphingosine-1-phosphate contributes to intracellular Ca(2+) homeostasis by maintaining basal NHE-1 activity and controls simultaneously myofibril Ca(2+) sensitivity through its inhibitory effect on adenylate cyclase. Cardioprotection by ischemic precondtioning depends on intact S1P1 signaling. These key findings on S1P1 functions in cardiac physiology may offer novel therapeutic approaches to cardiac diseases.
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