Cardiovascular diseases like the coronary heart disease are one of the main causes of death in Germany. The clinical manifestation of coronary heart diseases between men and women differs in age and clinical outcome during invasive therapies (1).
One main molecular reason is seen in the ambivalent effects of estrogens and androgens on endothelial cells and myocytes. In contrast to androgens, estrogens seem to inhibit the hypertrophy of cardiomyocytes while stimulating the expression of the atrial natriuretic peptide (ANP). Estrogens act as modulators in various intracellular signal pathways with cardio protective effects (e.g. phosphoinositide 3-kinases (PI3K), glycogen synthase kinase (GSK3), L-type Ca-channel, peroxisome proliferator-activated receptor (PPAR), serine/threonine kinases (AKT)). Signal pathways influenced by estrogens or androgens are closely related to gene expression, which is important for the energy metabolism of the cell. Consequential assumptions are sex specific difference in myocardial hypertrophy and differences in pathways, which are essential for the ATP production for the muscle contraction.
The objective of our study is to reconstruct the metabolic network of the cardiomyocyte and identify metabolic changes in hypertrophic cardiomyocytes with a systems biological approach.
Researchers
Anja Karlstädt
Prof. Hermann-Georg Holzhütter
in cooperation with AG Regitz-Zagrosek, Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR).