DFG Research Group (FOR 1054) "Sex specific mechanisms in myocardial hypertrophy" DFG;

Koordinator: Vera Regitz-Zagrosek, 2011-2016

Partner: Charité, MDC, DHZB

The research group assembles 8 working groups of excellent scientists of Charité-Universitätsmedizin Berlin, the German Heart Institute Berlin (DHZB) and Max-Delbrück-Center for Molecular Medicine (MDC) and achieved successfully the second funding period. The main goal of that research group is the analysis of gender differences in the adaptation of the heart to mechanical stress. We perform a series of mechanical analysis using cell cultures and animal models. This includes models of physiological and pathological myocardial stress, e.g. strength training and hypertension.

The role of sexual hormones and their receptors selectively analysed. Moreover, the effect of sex hormones on the lipid turnover is investigated. The working group of Prof. Vera Regitz-Zagrosek at the GiM collaborates with clinical projects and focuses here especially on gender differences in myocardial reaction to overload due to aortic valve disease.Based on our previous findings, we hypothesize that estrogen (E2) and its receptors ERα and ERb modify the cardiac response to mechanical load by regulating mitochondrial function and energy metabolism. AKT signaling and key regulators of mitochondrial function and metabolic genes are probably involved in these processes. We will investigate sex differences in mouse models of physiological and pathological MH. This involves the analysis of sex-specific regulation of genes encoding proteins involved in energy metabolism, micro-RNAs and protein patterns. Further, we analyse the mechanisms leading to the sex differences in the cardiac phenotypes.

In cell culture experiments we will dissect the effects of E2-activated ERα and ERb on key factors that control mitochondrial gene expression, such as MEF2, PGC-1α and PPARs and we will determine their expression level and/or transcriptional activity after selective gene silencing of ERs. The project will identify sex-specific MH mechanisms with therapeutic potential relevant to both genders. Responsible investigators: Vera Regitz-Zagrosek, Professor und Carola Schubert, PhD