ArticleCirculation2013
β1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 78 citations in OpenAlex.
- Unveiling the Therapeutic Mechanisms of Chinese Herbs in Heart Failure: Integrating Network Pharmacology, Molecular Docking, and Simulation Analysis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.Molecular imaging and biology · 2025Article
- Exploration of serum biomarkers in heart failure patients with preserved and reduced ejection fractions through analysis of heterogeneity.Biochemistry and biophysics reports · 2025Article
- Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.Theranostics · 2025Article
- Chlorogenic acid attenuates cardiac hypertrophy via up-regulating Sphingosine-1-phosphate receptor1 to inhibit endoplasmic reticulum stress.ESC heart failure · 2024Article
- Article
- Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases.Biomolecules · 2023Review
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.Scientific reports · 2022Article
- Chronic treatment with serelaxin mitigates adverse remodeling in a murine model of ischemic heart failure and modulates bioactive sphingolipid signaling.Scientific reports · 2022Article
- Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate.International journal of molecular sciences · 2022Review
- Endothelial Retargeting of AAV9 In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Sphingolipid metabolism and signaling in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum.The Journal of cell biology · 2021Article
- 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
- Human Cell Modeling for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- The role of sphingosine 1-phosphate and its receptors in cardiovascular diseases.Journal of cellular and molecular medicine · 2020Review
- 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
- Clinical value of detecting autoantibodies against βJournal of geriatric cardiology : JGC · 2020Article
- Emerging Role of Compartmentalized G Protein-Coupled Receptor Signaling in the Cardiovascular Field.ACS pharmacology & translational science · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G-protein-coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein-coupled receptor kinase-2, which triggers desensitization and downregulation processes. Although classic signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply result in opposing action on cAMP production, in this report we have uncovered a direct interaction between these 2 receptors, with regulatory involvement of G-protein-coupled receptor kinase-2. METHODS AND
resultsIn HEK (human embryonic kidney) 293 cells overexpressing both β1AR and S1PR1, we demonstrated that β1AR downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1 agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a β-adrenergic receptor agonist) treatment. This cross talk between these 2 distinct G-protein-coupled receptors appears to have physiological significance, because they interact and show reciprocal regulation in mouse hearts undergoing chronic β-adrenergic receptor stimulation and in a rat model of postischemic heart failure.
conclusionsWe demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious β1AR overstimulation in heart failure.
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.