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

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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).