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Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion.
Cardiovasc Res. 2009 Jul 15; 83(2):285-93.CR

Abstract

AIMS

Several experimental studies have demonstrated protection against cardiac ischaemia-reperfusion injury achieved by pre-treatment with exogenous sphingosine-1-phosphate (S1P). We tested the hypothesis that pharmacological S1P receptor agonists improve recovery of function when applied with reperfusion.

METHODS AND RESULTS

Isolated rat cardiomyocytes were stimulated with exogenous S1P, the selective S1P1 receptor agonist SEW2871, or the S1P1/3 receptor agonist FTY720. Western blot analysis was performed to analyse downstream signalling pathways. Ischaemia-reperfusion studies were conducted in rat cardiomyocytes, isolated Langendorff-perfused rat hearts, and in human myocardial muscle strip preparations to evaluate the effect of S1P receptor agonists on cell death and recovery of mechanical function. All S1P receptor agonists were able to activate Akt. This was associated with transactivation of the epidermal growth factor receptor. In isolated cardiomyocytes, selective stimulation of the S1P1 receptor by SEW2871 induced protection against cell death when administered either before or after ischaemia-reperfusion. In isolated rat hearts, treatment with FTY720 during reperfusion attenuated the rise in left ventricular end-diastolic pressure (LVEDP) and improved the recovery of left ventricular developed pressure without limiting infarct size. However, selective S1P1 receptor stimulation did not improve functional recovery but rather increased LVEDP. Additional experiments employing a human myocardial ischaemia-reperfusion model also demonstrated improved functional recovery induced by FTY720 treatment during reperfusion.

CONCLUSION

Pharmacological S1P receptor agonists have distinct effects on ischaemia-reperfusion injury. Their efficacy when applied during reperfusion makes them potential candidates for pharmaceutical postconditioning therapy after cardiac ischaemia.

Authors+Show Affiliations

Department of Internal Medicine I, University of Würzburg, Medizinische Klinik und Poliklinik I, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. hofmann_u2@klinik.uni-wuerzburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19416991

Citation

Hofmann, Ulrich, et al. "Protective Effects of Sphingosine-1-phosphate Receptor Agonist Treatment After Myocardial Ischaemia-reperfusion." Cardiovascular Research, vol. 83, no. 2, 2009, pp. 285-93.
Hofmann U, Burkard N, Vogt C, et al. Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion. Cardiovasc Res. 2009;83(2):285-93.
Hofmann, U., Burkard, N., Vogt, C., Thoma, A., Frantz, S., Ertl, G., Ritter, O., & Bonz, A. (2009). Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion. Cardiovascular Research, 83(2), 285-93. https://doi.org/10.1093/cvr/cvp137
Hofmann U, et al. Protective Effects of Sphingosine-1-phosphate Receptor Agonist Treatment After Myocardial Ischaemia-reperfusion. Cardiovasc Res. 2009 Jul 15;83(2):285-93. PubMed PMID: 19416991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion. AU - Hofmann,Ulrich, AU - Burkard,Natalie, AU - Vogt,Carolin, AU - Thoma,Annemarie, AU - Frantz,Stefan, AU - Ertl,Georg, AU - Ritter,Oliver, AU - Bonz,Andreas, Y1 - 2009/05/05/ PY - 2009/5/7/entrez PY - 2009/5/7/pubmed PY - 2009/9/9/medline SP - 285 EP - 93 JF - Cardiovascular research JO - Cardiovasc. Res. VL - 83 IS - 2 N2 - AIMS: Several experimental studies have demonstrated protection against cardiac ischaemia-reperfusion injury achieved by pre-treatment with exogenous sphingosine-1-phosphate (S1P). We tested the hypothesis that pharmacological S1P receptor agonists improve recovery of function when applied with reperfusion. METHODS AND RESULTS: Isolated rat cardiomyocytes were stimulated with exogenous S1P, the selective S1P1 receptor agonist SEW2871, or the S1P1/3 receptor agonist FTY720. Western blot analysis was performed to analyse downstream signalling pathways. Ischaemia-reperfusion studies were conducted in rat cardiomyocytes, isolated Langendorff-perfused rat hearts, and in human myocardial muscle strip preparations to evaluate the effect of S1P receptor agonists on cell death and recovery of mechanical function. All S1P receptor agonists were able to activate Akt. This was associated with transactivation of the epidermal growth factor receptor. In isolated cardiomyocytes, selective stimulation of the S1P1 receptor by SEW2871 induced protection against cell death when administered either before or after ischaemia-reperfusion. In isolated rat hearts, treatment with FTY720 during reperfusion attenuated the rise in left ventricular end-diastolic pressure (LVEDP) and improved the recovery of left ventricular developed pressure without limiting infarct size. However, selective S1P1 receptor stimulation did not improve functional recovery but rather increased LVEDP. Additional experiments employing a human myocardial ischaemia-reperfusion model also demonstrated improved functional recovery induced by FTY720 treatment during reperfusion. CONCLUSION: Pharmacological S1P receptor agonists have distinct effects on ischaemia-reperfusion injury. Their efficacy when applied during reperfusion makes them potential candidates for pharmaceutical postconditioning therapy after cardiac ischaemia. SN - 1755-3245 UR - https://www.unboundmedicine.com/medline/citation/19416991/Protective_effects_of_sphingosine_1_phosphate_receptor_agonist_treatment_after_myocardial_ischaemia_reperfusion_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvp137 DB - PRIME DP - Unbound Medicine ER -