Project 9: The role of ROS in HFpEF

PI Göttingen: G. Hasenfuß; PI London: A.M. Shah; PhD student: Surabhi Swarnkar

Scientific background and preliminary results

Heart failure is a major global health burden. More than 50% of patients with heart failure symtoms present with diastolic dysfunction and relatively well-preserved systolic function. This disease entity is termed „heart failure with preserved ejection fraction“ (HFpEF) and imposes significant morbidity and mortality (Udelson JE 2011; Borlaug BA 2014). However, cellular mechanisms underlying this condition are poorly understood and HFpEF-specific treatment options are lacking. The production of reactive oxygen species (ROS) appears to be an important mechanism in the pathophysiology of diastolic dysfunction and HFpEF (Murdoch CE et al. 2014); however, mitochondrial versus cytoplasmic contributions in this context have not yet been studied in vivo. Thus, HFpEF stress using the well-established DOCA-salt hypertension model will be applied to previously generated redox biosensor mice, which allow to separately quantify changes in mitochondrial and cytoplasmic redox potentials (Swain et al. 2016). Additionally, these mice will undergo exercise-training as exercise has been shown to improve diastolic function HFpEF patients (Edelmann F et al. 2011).

Hypotheses and aims

We hypothesize that this is due to increased antioxidant signaling. This will help to better understand the distinct role of ROS in HFpEF pathophysiology.

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