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Enhanced cardiac S100A1 expression improves recovery from Gglobal Ischemia-reperfusion injury

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1...

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Main Authors: Jungi, Silvan (Author) , Fu, X. (Author) , Segiser, A. (Author) , Busch, Martin (Author) , Most, Patrick (Author) , Fiedler, M. (Author) , Carrel, T. (Author) , Tevaearai Stahel, H. (Author) , Longnus, S. L. (Author) , Most, Henriette (Author)
Format: Article (Journal)
Language:English
Published: 1 February 2018
In: Journal of cardiovascular translational research
Year: 2018, Volume: 11, Issue: 3, Pages: 236-245
ISSN:1937-5395
DOI:10.1007/s12265-018-9788-y
Online Access:Verlag, Volltext: https://doi.org/10.1007/s12265-018-9788-y
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Author Notes:S. Jungi, X. Fu, A. Segiser, M. Busch, P. Most, M. Fiedler, T. Carrel, H. Tevaearai Stahel, S.L. Longnus, Henriette Most
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Summary:Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.
Item Description:Gesehen am 07.11.2019
Physical Description:Online Resource
ISSN:1937-5395
DOI:10.1007/s12265-018-9788-y

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