Sphingosine-1-phosphate (S1P) activates STAT3 to protect against de novo acute heart failure (AHF)
| Autor: | Sandrine Lecour, Gaurang Deshpande, Aqeela Imamdin, Lionel H. Opie |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor medicine.medical_specialty Cardiotonic Agents Blood Pressure 030204 cardiovascular system & hematology In Vitro Techniques General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Ventricular Dysfunction Left 0302 clinical medicine Heart Rate Sphingosine Internal medicine Heart rate medicine Animals In patient Rats Long-Evans Sphingosine-1-phosphate General Pharmacology Toxicology and Pharmaceutics Phosphorylation STAT3 Cardioprotection Heart Failure biology business.industry De novo acute General Medicine Tyrphostins medicine.disease Rats 030104 developmental biology chemistry Heart failure Acute Disease STAT protein biology.protein Cardiology Lysophospholipids business |
| Zdroj: | Life sciences. 196 |
| ISSN: | 1879-0631 |
| Popis: | Acute heart failure (AHF) is a burden disease, with high mortality and re-hospitalisations. Using an ex-vivo model of AHF, we have previously reported that sphingosine-1-phosphate (S1P) confers cardioprotection. However, the mechanisms remain to be elucidated. In the present study, we aimed to examine the role of the cardioprotective signal transducer and activator of transcription 3 (STAT3) in S1P mediated improved functional recovery in AHF.Isolated hearts from male Long-Evans rats were subjected to hypotensive AHF for 35 min followed by a recovery phase of 30 min (n ≥ 4/group). S1P (10 nM) was given during either the hypotensive or the recovery phase with/without an inhibitor of STAT3, AG490. Functional parameters were recorded throughout the experiment.Following an AHF insult, S1P, given during the recovery phase, improved the heart rate (HR) compared to the control (175.2 ± 30.7 vs. 71.6 ± 27.4 beats per minute (BPM); p 0.05), with no changes in the left ventricular developed pressure. This effect was associated with an increase in phosphorylated STAT3 levels in the nucleus. Addition of AG490 with S1P abolished the cardioprotective effect of S1P (42.3 ± 17.1 vs. 148.8 ± 26.4 BPM for S1P; p 0.05).Our data suggest that S1P protects in an ex-vivo rat heart model of AHF by activation of STAT3 and provide further evidence for the usage of S1P as a potential therapy in patients suffering from AHF. |
| Databáze: | OpenAIRE |
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