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HFpEF is a heterogenous clinical syndrome with incomplete mechanistic understanding. To improve our understanding of the molecular disease mechanisms, we will perform in-depth proteomic analyses of well phenotyped HFpEF patients and our central HFD+L-NAME mouse model both under resting conditions as well as under disease mitigating exercise conditions. We will also explore disease-specific alterations in proteostasis by studying protein ubiquitination in heart and skeletal muscle tissues in a sex-specific manner. The acquired molecular signatures will be bioinformatically connected to changes in key clinical and pathophysiological readouts to improve patient stratification, identify new biomarkers and potential new therapeutic targets.
Graphical Abstract: PreHFpEF and HFpEF patients (n = 400 each) with deep clinical phenotyping in Z02 (Pieske, Edelmann, Rauch, Tschöpe) and Z01 (Heinzel, Alogna, Gotthardt) will undergo plasma protein profiling. HFpEF patients and HFD+L-NAME mice will be enrolled in exercise training and subgroups undergo cardiac and skeletal muscle proteomic profiling. In vivo/clinical phenotyping and matched proteome/modificome analysis will be integrated in functional models and patient stratification.
Schafstedde M, Nordmeyer J, Berger F, Knosalla C, Mertins P, Ziehm M, Kirchner ML, Regitz-Zagrosek V, Kuehne T, Kraus M, Nordmeyer S. Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement. Am J Physiol Heart Circ Physiol. 2022 Nov 1;323(5):H949-H957. doi: 10.1152/ajpheart.00288.2022. Epub 2022 Oct 7. PMID: 36206048; PMCID: PMC9621711.