S100A4: Evaluation eines neuen Kandidatenproteins für die Prävention kardialen Zelltods und Steigerung der Regenerationsfähigkeit im ischämischen Myokard

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The progressive nature of ischemic cardiomyopathy appears to be dictated in part by the inability of the myocardium to regenerate and to compensate the continuous loss of cardiac myocytes. New treatments that target disease mechanisms at the cellular and wholeorgan level are needed to halt and reverse the consequences of this disease. S100A4 is a calcium binding cardiac protein shown to protect cardiac myocytes from cell death in vitro. In addition, it has been proven that S100A4 promotes cardiomyogenesis and induces differentiation and proliferation of stem cells in vitro. However, the underlying molecular mechanism and the potential beneficial effects of S100A4 are still unknown. The central hypothesis of this proposal is therefore that S100A4 protein exerts both favourable effects on survival of myocytes and improves cardiac regeneration in the infarcted heart. In particular, this proposal aims to determine (1) the molecular mechanism and signalling cascades of S100A4 underlying the antiapoptotic effect, (2) the significance of S100A4 on proliferation and survival of stem cells with the ultimate goal (3) of translating these findings in an experimental therapeutic strategy in preclinical disease models.