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02.01.2019 | Original Article | Ausgabe 6/2019

Heart and Vessels 6/2019

Involvement of sphingosine-1-phosphate receptors 2/3 in IR-induced sudden cardiac death

Heart and Vessels > Ausgabe 6/2019
Xiaojia Zhang, Deqing Chen, Jiaqi Wang, Jinding Liu, Hualin Guo, Gengqian Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00380-018-01323-8) contains supplementary material, which is available to authorized users.
Xiaojia Zhang and Deqing Chen contributed equally to this work.

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It has been demonstrated that S1P receptors affect heart ischaemia–reperfusion (IR) induced injury. However, whether S1P receptors affect IR-induced cardiac death has not been investigated. The aim of this paper is to demonstrate the role of S1P receptors in IR-induced cardiac death. Healthy adult male Sprague–Dawley rats were assigned to the following groups: non-operation control group, sham operation group, IR group, IR group pretreated with DMSO, IR group pretreated with S1P3 agonist, IR group pretreated with an antagonist of S1P3, IR group pretreated with S1P2 and S1P3 antagonists, IR group pretreated with heptanol and antagonists of S1P2/3, and IR group pretreated with Gap26 and antagonists of S1P2/3 (heptanol acts as a Cx43 uncoupler and the mimic peptide Gap26 as Cx43 blocker). The groups with S1P2 or S1P3 agonist application before reperfusion were used to assess whether these can be used for therapy of IR. The haemodynamics, electrocardiograms (ECG), infarction area, and mortality rates were recorded. Immunohistological connexin 43 (Cx43) expression in the heart was detected in each group. Blocking S1P2/3 receptors with specific antagonists resulted in an increment of IR-induced mortality, increased infarction size, redistribution of Cx43 expression, as well as affecting the heart function. The infarction size, heart function, and mortality were totally or partially restored in the S1P2, S1P3 agonist-pretreated IR group, and the heptanol/Gap26-treated S1P2/3-blocked IR group. The S1P receptor S1P2/3 and Cx43 are involved in the IR-induced cardiac death.

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Supplementary file1 (DOCX 22 kb)
Supplementary file 2 (TIFF 491 kb)
Supplementary file 3 (TIFF 2074 kb)
Supplementary file 4 (TIFF 132 kb)
Supplementary file 5 (TIFF 8661 kb)
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