Effekte einer endothel-spezifischen PGC-1alpha Deletion auf die Modulation der Gefäßfunktion

跨膜共激活因子PGC-1 α在线粒体生物发生和功能中起着重要作用。来自我们自己的小组和其他人的数据表明，AMP激活的蛋白激酶（AMPK），这是已知的细胞代谢的中央调节器，在血管系统中起着保护作用。由于PGC-1 α是AMPK最重要的下游靶点之一，我们假设内皮PGC-1 α的缺失在血管紧张素II输注过程中损害血管功能，并且NO信号传导/氧化应激（假设1）或血管炎症（假设3）的变化在此过程中起关键作用。线粒体靶向抗氧化剂mitoTEMPO的体内应用应确定线粒体活性氧是否在此过程中有因果关系。在另外两个方案中，我们计划研究PGC-1 α在运动血管保护作用中的作用。我们假设内皮细胞PGC-1 α可能影响运动介导的血管活性氧产生和NO信号的变化（假设2），这可能解释PGC-1 α相关的新血管生成和血管老化的变化（假设4）。

The transkriptional coactivator PGC-1alpha plays a fundamental role in mitochondrial biogenesis and function. Data from our own group and others demonstrated that the AMP-activated protein kinase (AMPK), which is known as a central regulator of cell metabolism, plays a protective role in the vasculature. Since PGC-1alpha is one of the most important downstream targets of AMPK, we hypothesize that a deletion of endothelial PGC-1alpha impairs vascular function during angiotensin II infusion and that changes in NO signaling / oxidative stress (hypothesis 1) or vascular inflammation (hypothesis 3) play a key role in this process. In vivo application of the mitochondrial targeted antioxidant mitoTEMPO should determine whether mitochondrial reactive oxygen species are causally involved in this process. In two additional protocols we plan to investigate the role of PGC-1alpha regarding the vascular protective effects of exercise. We hypothesize that endothelial PGC-1alpha may affect exercise-mediated changes in vascular reactive oxygen species production and NO-signaling (hypothesis 2), which may account for PGC-1alpha related changes in neoangiogenesis and vascular aging (hypothesis 4).