Abstract

Aim: Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models.Methods and Results: In this study, we investigated the localization of S1PRs in human heart samples from cardiac surgery department, University of Verona Hospital and rat samples. Immunohistochemical investigation of paraffin-embedded sections illustrated diffused staining of the myocardial samples from human and rat. The signals of the human heart were similar to those of the rat heart in all chambers of the heart. The immunohistochemical expression levels correlated well with the results of RT-PCR-based analysis and western blotting. We confirmed by all techniques that S1PR1 expressed strongly as compared to S1PR3, and are uniformly distributed in all chambers of the heart with no significant difference in human and rat myocardial tissue. S1PR2 expression was significantly weak while S1PR4 and S1PR5 were not detectable in RT-PCR results in both human and rat heart.Conclusion: These results indicate that experimental studies using S1PR agonists on rat models are more likely to have a potential for translation into clinical studies, and second important information revealed by this study is, S1P receptor agonist can be used for cardioprotection in global ischemia-reperfusion injury.

Highlights

  • The S1P is known lysolipid mediator for more than two decades to play a role in cellular changes, including differentiation, proliferation, migration, contraction, and survival (Zhang et al, 1991; Hannun, 1996; Hannun and Obeid, 1997; Spiegel et al, 1998; Ishii et al, 2004; Chun et al, 2010)

  • Mild enhanced expression of S1PR1 was observed in the human heart with statistically no difference in any heart chamber and expression were similar in both human and rat myocardial tissue mRNA

  • The mRNA level of SIPR2 and S1PR3 were found uniformly distributed in all chambers of human and rat heart

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Summary

Introduction

The S1P is known lysolipid mediator for more than two decades to play a role in cellular changes, including differentiation, proliferation, migration, contraction, and survival (Zhang et al, 1991; Hannun, 1996; Hannun and Obeid, 1997; Spiegel et al, 1998; Ishii et al, 2004; Chun et al, 2010). Sphingosine 1-Phosphate Receptors Expression in Heart years to induce cellular responses, including proliferation, migration, contraction, and intracellular calcium mobilization (Means and Brown, 2009). It can be used to block S1P actions that indicate that S1P works through GCPRs. EDG 1, EDG3, EDG5, EDG6, and EDG8 receptors family of GCPRs showed high affinity for S1P (Hla et al, 2000). EDG 1, EDG3, EDG5, EDG6, and EDG8 receptors family of GCPRs showed high affinity for S1P (Hla et al, 2000) It is well-established that the activation of these GCPRs is the mechanism through which most of the biological responses elicit with S1P (Means and Brown, 2009). We investigated S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5 expression in different chambers of the heart

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