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Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury

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Abstract

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.

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Funding

This work was supported by a Project Grant from the Swiss National Science Foundation (310030_149730/1 to S.L.) and a Research Grant from the Ruth & Arthur Scherbarth Foundation (to H.M. and S.L.), M.B. and P.M. receive funding via the German Center for Cardiovascular Research (DZHK).

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, Inselspital University Hospital, University of Bern, 3010, Bern, Switzerland

    S. Jungi, X. Fu, A. Segiser, T. Carrel, H. Tevaearai Stahel, S. L. Longnus & Henriette Most

  2. Section for Molecular and Translational Cardiology, Department of Cardiology, Pneumology and Angiology, Karl-Ruprechts University of Heidelberg, Heidelberg, Germany

    M. Busch & P. Most

  3. German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, Germany

    M. Busch & P. Most

  4. Center for Laboratory Medicine, Inselspital University Hospital, University of Bern, Bern, Switzerland

    M. Fiedler

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  1. S. Jungi
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  9. S. L. Longnus
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Correspondence to Henriette Most.

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Associate Editor Saptarsi Haldar oversaw the review of this article

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Jungi, S., Fu, X., Segiser, A. et al. Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury. J. of Cardiovasc. Trans. Res. 11, 236–245 (2018). https://doi.org/10.1007/s12265-018-9788-y

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