ArticleCardiovascular research2016
Sphingosine-1-phosphate reduces ischaemia-reperfusion injury by phosphorylating the gap junction protein Connexin43.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- The connexin 43 carboxyl terminal mimetic peptide αCT1 prompts differentiation of a collagen scar matrix in humans resembling unwounded skin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Trial
- Nanobody-based Pannexin1 channel inhibitors increase survival after cardiac ischemia/reperfusion.Cell and tissue research · 2025Article
- Targeted immunotherapy with sphingosine-1-phosphate improves myocardial contractility and mitochondrial function in a novel murine ex vivo perfusion and transplantation model.The Journal of thoracic and cardiovascular surgery · 2025Article
- Activation of sphingosine-1-phosphate receptors can relieve myocardial ischemia-reperfusion injury by mitigating oxidative stress and ferroptosis in cardiomyocytes.International journal of biological sciences · 2025Article
- Cardiac Fibroblasts Enhance MMP2 Activity to Suppress Gap Junction Function in Cardiomyocytes.Applied biochemistry and biotechnology · 2024Article
- The activation of P38MAPK Signaling Pathway Impedes the Delivery of the Cx43 to the Intercalated Discs During Cardiac Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2024Article
- High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction.International journal of molecular sciences · 2024Review
- The role and mechanisms of microvascular damage in the ischemic myocardium.Cellular and molecular life sciences : CMLS · 2023Review
- Dissecting the Therapeutic Mechanisms of Sphingosine-1-Phosphate Receptor Agonism during Ischaemia and Reperfusion.International journal of molecular sciences · 2023Article
- Review
- Lipocalin family proteins and their diverse roles in cardiovascular disease.Pharmacology & therapeutics · 2023Review
- Article
- GJA1-20k and Mitochondrial Dynamics.Frontiers in physiology · 2022Review
- Benefits of SGLT2 inhibitors in arrhythmias.Frontiers in cardiovascular medicine · 2022Review
- Sphingolipid metabolism and signaling in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins.Biomedicines · 2021Review
- A state-of-the-art review of the current role of cardioprotective techniques in cardiac transplantation.Interactive cardiovascular and thoracic surgery · 2021Review
- Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.Basic research in cardiology · 2021Article
- Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection.Biomolecules · 2020Review
- Mitochondrial ion channels as targets for cardioprotection.Journal of cellular and molecular medicine · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
aimIncreasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDLs). HDL binding to receptors at the surface of cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate the pathways by which the sphingosine-1-phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischaemia-reperfusion (I/R). METHODS AND
resultsApolipoprotein M (ApoM) transgenic (Apom-Tg) mice, in which plasma S1P is increased by 296%, and wild-type (WT) mice were subjected to in vivo I/R. Infarct size, neutrophil infiltration into the infarcted area, and serum Troponin I were less pronounced in Apom-Tg mice. In vitro experiments suggest that this cardioprotection depends on direct effects of S1P on cardiomyocytes, whereas leucocyte recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce I/R injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap junction protein Connexin43 (Cx43) on Serine368 (S368), which was mediated by S1P2 and S1P3, but not by S1P1, receptors in cardiomyocytes. Finally, S1P-induced reduction of infarct size after ex vivo I/R was lost in hearts of mice with a truncated C-terminus of Cx43 (Cx43(K258/KO)) or in which the S368 is mutated to a non-phosphorylatable alanine (Cx43(S368A/S368A)).
conclusionOur study reveals an important molecular pathway by which modulating the apoM/S1P axis has a therapeutic potential in the fight against I/R injury in the heart.
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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.