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

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

Journal of cardiovascular translational research (2018-02-03)
S Jungi, X Fu, A Segiser, M Busch, P Most, M Fiedler, T Carrel, H Tevaearai Stahel, S L Longnus, Henriette Most
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Creatine Phosphokinase from rabbit muscle, Type I, salt-free, lyophilized powder, ≥150 units/mg protein
Sigma-Aldrich
Hexokinase from Saccharomyces cerevisiae, Type F-300, lyophilized powder, ≥130 units/mg protein (biuret)