Linking metabolism, mechanotransduction and endothelial dysfunction in HFpEF (A03)

• Subject Area: Cardiology, Angiology ; Animal Physiology and Biochemistry ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437531118

Heart failure with preserved ejection fraction (HFpEF) is linked to co-morbidity induced systemic inflammation causing endothelial dysfunction and perturbed endothelial-myocardial signaling leading to functional and structural alteration in myocardium. Hallmarks of endothelial dysfunction in HFpEF are decreased endothelial nitric oxide synthase (eNOS) and increased reactive oxygen species (ROS) and TGFb production, finally leading to myofibrosis of left ventricular wall and impaired elasticity of the neighboring vessels. In our project, we aim to address the function of endothelial YAP/TAZ (YT) signaling, menchanotranscducers shown to respond to a variety of signals and to target the level of TGFb/BMP output under challenging hemodynamic conditions in the development of HFpEF. We combine mouse, zebrafish, and iPSC models in combination with ex vivo microfluidics to assess inflammatory, physical, and metabolic stress in endothelial cells (EC) and examine endothelial cardiomyocyte signaling and potential pharmacological intervention.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1470: Multilevel mechanistic characterisation of Heart Failure with Preserved Ejection Fraction - Towards a novel classification of HFpEF for targeted therapies
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Holger Gerhardt; Professor Dr. Ulf Landmesser