ArticleAmerican journal of physiology. Heart and circulatory physiology2011
S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
- Plasma metabolomic profiling reveals lipid biomarkers for early detection of exercise-induced myocardial ischemia.Medicine · 2026Article
- PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.Molecular imaging and biology · 2025Article
- Ceramide in Coronary Artery Disease: Troublesome or Helpful Future Tools in the Assessment of Risk Prediction and Therapy Effectiveness?Metabolites · 2025Review
- Deciphering the role of sphingosine 1-phosphate in central nervous system myelination and repair.Journal of neurochemistry · 2025Review
- The sphinx helps to answer the riddle of cardiac regeneration.Trends in endocrinology and metabolism: TEM · 2024Article
- High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction.International journal of molecular sciences · 2024Review
- Sphingosine 1-Phosphate Lyase in the Developing and Injured Nervous System: a Dichotomy?Molecular neurobiology · 2023Review
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- Sphingosine-1-phosphate improves outcome of no-reflow acute myocardial infarction via sphingosine-1-phosphate receptor 1.ESC heart failure · 2023Article
- miR-542-5p targets c-myc and negates the cell proliferation effect of SphK1 in intestinal epithelial cells.American journal of physiology. Cell physiology · 2023Article
- Potential Drug Targets for Ceramide Metabolism in Cardiovascular Disease.Journal of cardiovascular development and disease · 2022Review
- Sphingosine 1-phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids.Clinical and translational medicine · 2022Article
- S1P Lyase Inhibition Starting After Ischemia/Reperfusion Improves Postischemic Cardiac Remodeling.JACC. Basic to translational science · 2022Article
- Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate.International journal of molecular sciences · 2022Review
- Sphingolipid metabolism and signaling in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- A Bioassay Using a Pentadecanal Derivative to Measure S1P Lyase Activity.International journal of molecular sciences · 2021Article
- U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study.Lipids in health and disease · 2020Article
- Sphingolipids in the Heart: From Cradle to Grave.Frontiers in endocrinology · 2020Review
- Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes.Cell death & disease · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia (n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls (n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity (n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts (n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P₁ and S1P₃ receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury.
Indexed as
Identifiers
What OpenQuestion holds
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.