PhD Scientific Days 2020

Theoretical and Translational I. Lectures

Dual Effect of S1P3 Receptors on Myocardial Functions

Előadó neve

Dr. Wafa, Dina

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

+36306369069

Előadó e-mail címe

dina.wafa.93@gmail.com

Az előadás címe

Dual Effect of S1P3 Receptors on Myocardial Functions

Szerző(k) neve és munkahelye

Wafa D, Koch N, Kovacs J, Kerek M, Benyo Z, Miklos Zs.
Institute of Translational Medicine, Semmelweis University, Budapest, Hungary

Szekció

Theoretical and Translational I. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: In acute coronary syndrome (ACS) activated platelets release numerous bioactive mediators, such as sphingosine-1-phosphate (S1P) during the thrombotic occlusion of coronaries. These may influence the severity of ischemia/reperfusion (I/R) injury. S1P is a lysophospholipid mediator which regulates diverse biological processes through its specific receptors (S1P1-5). Among others, S1P has been shown to be protective against I/R injury in the heart. On the other hand, some studies highlighted its potential constrictive effects in the coronaries.
Aims: When S1P is released in ACS in large amounts, its favorable and potentially deleterious effects may be conflicted. We aimed to delineate how these conflicting S1P actions indeed affect postischemic cardiac injury.
Method: Experiments were conducted on isolated Langendorff-perfused murine hearts. Left ventricular pressure and coronary flow (CF) were continously monitored. After equilibration, S1P (10-6 M) or its vehicle was infused to the perfusion line for 5 minutes. Then either wash-out or a 20-minute global ischaemia/2-hour reperfusion protocol was applied. Size of the infarcted myocardium was determined through TTC staining. Experiments were carried out in WT, S1P2 and S1P3 gene-deficient C57/Bl6 mice strains.
Results: Administration of S1P reduced CF by 1.95±0.33 ml/min and compromised left ventricular contractile performance in WT hearts. These effects in S1P2 KO mice were similar. However, in S1P3 KO hearts the S1P induced CF reduction (0.93±0.10 ml/min), and decline in contractile function were diminished. In the I/R experiments, postischemic functional recovery was weaker and infarct size was larger in S1P3 KO hearts. Preischemic S1P treatment worsened the recovery of CF and contractile function both in WT and S1P3 KO hearts.
Conclusion: In this study we observed a massive CF reducing effect of S1P that resulted in the drop of the contractile function mediated via S1P3 receptor. We verified the role of S1P3 receptor in cardioprotection, but not the S1P pretreatment that just further exacerbated I/R-induced myocardial damage. These results may suggest that S1P derived from the myocardium acts on different sites compared to S1P derived from vessels. The latter scenario can occur during ACS when a large amount of S1P is released due to platelet activation.

Additional Information

Zsuzsanna Miklós
miklos.zsuzsanna@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4079

Start

10:50

End

11:05

Authors (legacy)

Wafa D, Koch N, Kovacs J, Kerek M, Benyo Z, Miklos Zs.
Institute of Translational Medicine, Semmelweis University, Budapest, Hungary