Deciphering the role of an E3 ubiquitin ligase HectD3 in cardiac pathophysiology

Project start
Institution: Universitätsklinikum Schleswig-Holstein Campus Kiel
Applicant: Ashraf Rangrez
EKFS funding line: First and Second Applications
Image: Action of HectD3 in the heart

Heart failure is the leading cause of mortality and hospitalizations worldwide and the numbers are ever increasing. Cardiac hypertrophy and chronic inflammation are two of the major molecular causes of a failing heart. Thus, either or both of these molecular mechanisms can potentially be therapeutically targeted. Based on our in vitro and preliminary in vivo studies, in this project, we propose a novel cardioprotective mechanism involving the E3 ubiquitin ligase HectD3, which links anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and Stat1. These encouraging preliminary results support the translational impact of HectD3, which will be tested in vivo in mouse models of ischemic and non-ischemic heart failure.

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