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

缺血性心肌病的进行性似乎部分是由于心肌不能再生和补偿心肌细胞的持续损失。需要在细胞和整个器官水平上针对疾病机制的新治疗方法来阻止和逆转这种疾病的后果。S100A4是一种钙结合心脏蛋白，在体外显示出保护心肌细胞免于细胞死亡。此外，已经证明S100A4在体外促进心肌形成并诱导干细胞的分化和增殖。然而，S100A4的潜在分子机制和潜在的有益作用仍然未知。因此，该提议的中心假设是S100A4蛋白对心肌细胞的存活发挥有利作用并改善梗死心脏中的心脏再生。具体而言，该提案旨在确定（1）S100A4抗凋亡作用的分子机制和信号级联，（2）S100A4对干细胞增殖和存活的重要性，最终目标是（3）将这些发现转化为临床前疾病模型的实验治疗策略。

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.