A systems and translational approach to titin dynamics in HFpEF (B04)

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

The giant protein titin forms the elastic backbone of the sarcomere. It is extensively spliced and phosphorylated to adjust cardiac filling in health and disease. Here, we will combine our genetic with interventional animal models and human engineered heart tissue to dissect titin’s contribution to cardiac growth, metabolism, and filling and its relation to heart failure with preserved ejection fraction (HFpEF). Our focus on titin biomechanics and isoform expression in male versus female will contribute to an improved mechanistic understanding of HFpEF, assessment of diastolic dysfunction, and the adaptation of titin based stiffness as a basis for targeted therapy.

• 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 Head: Professor Dr. Michael Gotthardt