The impact of oxidative post-translational modifications on vascular function and angiocrine signaling
Oxidative-modifications of reactive cysteine residues in susceptible proteins determine endothelial cell fitness. During the first funding period we characterized the role of one oxidative post-translational modification (oxPTM) i.e. S-sulfhydration in the angiocrine regulation of vascular and cardiac homeostasis. In native human endothelial cells, we identified an age-related reduction in the cysteine S-sulfhydration as well as in the S-nitrosation of proteins, oxPTMs that differentially impact on cell function. Our preliminary data indicate that interfering with the generation of these oxPTMs alters adipose tissue phenotypes in mice. In this project we plan to identify S-nitrosated and S-sulfhydrated proteins in endothelial cells, endothelial cell-derived extracellular vesicles and neighbouring adipocytes, and to gain insight into how protein oxPTMs drive white adipose tissue responses to dietary challenge and aging.