Research projects

Principle Investigator: Prof. Ulrich Kintscher 

Investigator: Niklas Beyhoff

The cardiac function is mainly determined by its (intact) structural composition. Nearly all cardiovascular diseases are accompanied by changes of the cardiac microstructure („cardiac remodeling“), which can lead to an impairment of myocardial mechanics. The aim of this project is an improved understanding of these remodeling processes and their impact on myocardial mechanics in order to identify novel diagnostic methods. For this purpose, state-of-the-art imaging methods such as speckle-tracking echocardiography are utilized for further correlations with histological data and biomarkers.

Principle Investigators: Prof. Ulrich Kintscher
Investigators: Eleya Sameer
Funding: Else Kröner Fresenius Stiftung (EKFS)

Heart failure (HF) is a chronic, debilitating disease that impairs the ability of the heart to respond to increased demands for cardiac output. Recently, lipids have gained increasing interest as biomarkers, molecular mediators and therapeutic agents for various diseases including cardiovascular disease. Major contributors to this development have been new advanced technologies for the analysis of lipid species on a systems level by lipidomic profiling using sensitive mass spectrometry (MS) technologies. In parallel to these clinical/ technical developments, lipid species have been characterized as endogenous molecular mediators of cardiac morphology and function.
In our study we aim to investigate the role of circulating and cardiac lipids in the development of heart failure. For this, we will combine molecular, cellular and in-vivo approaches with state-of-the-art lipidomic profiling. We aim to identify new lipid mediators involved in the pathogenesis of chronic heart failure, and we want to understand how cellular lipids contribute to pathological responses under established cardiac stressors such as catecholamines.

Principle Investigators: Prof. Ulrich Kintscher and PD Anna Foryst-Ludwig
Investigators: Sarah Julia Qaiyumi
Funding: Charité

Our recently publish data indicate that Palmitoleic Acid (C16:1) mediate exercise-induced development of physiological cardiac hypertrophy. While the in vivo cardiac effects of palmitoleic acid have been investigated extensively, the fundamental molecular signaling of this fatty acid in cardiomyocytes remains widely unclear.
The finding that C16:1 promotes the phosphorylation of the AKT protein (Foryst-Ludwig et al.) is currently the only hint to how palmitoleic acid brings about these physiological cardiac growth processes. Therefore the target of this projects is to investigate the impact of C16:1 on the AKT/FOXO signaling pathway, using a variety of different molecular biology techniques, in order to fully grasp the cellular processes that are being triggered by C16:1  and how they ultimately bring out physiological cardiac hypertrophy.

Principle Investigators: PD Anna Foryst-Ludwig and Prof. Ulrich Kintscher
Investigators: Iris Betz, Sarah Brix
Funding: Charité

This project investigates the impact of palmitoleic acid (C16:1) on nuclear hormone receptors in the heart and especially its role in the development of physiologic hypertrophy. While we already know some of the effects on the heart in vivo the basic molecular signaling pathways of this fatty acid are still widely unknown.
Nuclear hormone receptors are part of a family of transcription factors which are located in cytosol and the nucleus of the cell. Classic ligands are hormones and lipids like e.g. steroids, androgens or vitamin A.
The aim of this project is to learn more about the signaling pathways and the pro-hypertrophic effects of this adipokine using novel sequencing methods. In cooperation with the Helmholtz-Institut Munich (H. Uhlenhaut) we are planning to explore the differential genome expression of C16:1 in cardiomyocytes.
By studying the effects palmitoleic acid on a molecular level we want to provide a new therapeutic option for patients suffering under heart hypertrophy and heart failure in the near future.

Principle Investigators: Prof. Ulrich Kintscher, PD Anna Foryst-Ludwig;
Investigators:  Zsofia Ban
Funding: Deutsche Forschungsgemeinschaft (DFG)

Estrogen-receptor alpha is one of the major regulators in metabolism and obesity. In this project we aimed to define the relevance of adipose tissue ERalpha during high-fat diet (HFD)-induced obesity using a tissue specific knock-out model (atERKO). To our surprise HFD did not affect metabolic parameters in atERKO but induced severe inflammation processes.
These infections were characterized by massive uterine neutrophil infiltration and marked reduction of "anti-inflammatory"-macrophages, pointing to an affected immune response. In parallel, this model was linked to high estradiol levels. Therefore, we decided to focus on the interactions between estrogen signaling and dietary lipids, especially in regard to the effects on the immune response. Indeed, we identified stearic acid (C18:0) in a lipid profiling approach, as a fatty acid prominently induced by HFD, which is able to induce ERalpha-acylation. We could show, that this fatty acid inhibits E2-induced transcriptional activity and estradiol-stimulated anti-inflammatory macrophage polarization.
In summary, we are interested in the molecular mechanism, by which dietary fatty acids can influence the function of nuclear hormone receptor such as estrogen receptor alpha.

Principle Investigator: Prof. Ulrich Kintscher
Investigators: Jana Grune
Funding: Bayer Pharma AG

Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. In consonance, current steroidal MR-antagonists such as spironolactone and eplerenone have been demonstrated to counteract negative MR actions, and to exhibit broad cardiovascular protective actions. However, current steroidal MR-antagonists are limited due to major side effects such as hyperkalemia, gynecomastia, impotence, erectile dysfunction and menstrual disturbances. Thus, new non-steroidal MR-antagonists with an improved efficacy/ side effect profile are currently developed.
Finerenone is a new non-steroidal MR antagonist developed from the chemical class of dihydropyridines (DHP) with high MR-potency and excellent MR-selectivity. Interestingly, DHP-based MR-antagonists display a distinct MR binding mode compared to steroidal antagonists resulting in an unstable receptor-ligand complex and distinct gene expression. Therefore, we were aiming to characterize the pharmacological actions of the non-steroidal MR-antagonist finerenone on cardiac gene expression, and on cardiac remodeling during pressure overload compared to steroidal MR-antagonists.