A08 - Metabolic reprogramming steered by ISGylation in HFpEF

Obesity is a major contributing feature of HFpEF and known to stimulate chronic low-grade inflammation. Cells respond to inflammatory stimuli with reprogramming of their posttranslational modification pathways and activation of protein ISGylation. This project pursues the hypothesis that chronic inflammation in cardiometabolic HFpEF provokes a metabolic adaptation of the heart possibly through the activation of the ISG15 machinery. By combining system biochemistry with computational metabolic modeling, this project will investigate the metabolic alterations occurring in the heart and define how the ISG15 system intersects in the regulation of cardiac metabolic capability in HFpEF.

Graphical Abstract: Impact of protein ISGylation on cardiac metabolism and reprogramming of the cardio-hepatic axis in cardiometabolic HFpEF.