B1: Role of cystathionine-y-lyase (CSE) in endothelial-myocardial interactions
Ingrid Fleming / Sofia Iris Bilbli
The cystathionine γ-lyase (CSE) metabolizes sulfur containing amino acids (L-cystathionine and L-cysteine) to pyruvate and hydrogen sulfide (H2S). We recently identified endothelial cell-, CSE-derived H2S as a regulator of the RNA binding protein HuR which regulates E-selectin and cathepsin S expression during atherogenesis in mice and humans. In this project we will determine the role of CSE in endothelial cell metabolism and function, as well as the role of endothelial cell CSE in regulating the metabolism and function of adjacent cardiomyocytes. Novel targets of H2S-derived polysulfides in endothelial cells and cardiomyocytes will be addressed by mapping the cellular “sulfhydromes”, and the importance of sulfur amino acid metabolism will be assessed by following the one carbon flux of CSE substrates to downstream metabolic precursors of the tricarboxylic acid cycle (i.e. pyruvate). The consequences of CSE deletion and H2S rescue with specific donors on gene regulation and protein function will be addressed to identify novel ways to target cardiac function and re-vascularization after injury.