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

转录辅激活因子PGC-1alpha在线粒体的生物发生和功能中起着重要作用。我们的研究小组和其他人的数据表明，amp激活的蛋白激酶（AMPK），被称为细胞代谢的中央调节剂，在脉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，我们假设内皮细胞pgc -1 α的缺失会在血管紧张素II输注过程中损害血管功能，而NO信号/氧化应激（假设1）或血管炎症（假设3）的变化在这一过程中起关键作用。在体内应用线粒体靶向抗氧化剂mitoTEMPO应该确定线粒体活性氧是否参与这一过程。在另外两个方案中，我们计划研究PGC-1alpha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），这可能解释了pgc -1 α在新生血管生成和血管衰老中的相关变化（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).