Sex-specific use of estrogen pathway modulation in human heart failure

There are major sex differences in heart failure. The overall hypothesis is that female sex or sex hormones lead to better maintenance of mitochondrial function, calcium handling and reduced fibrosis and apoptosis under stress. To investigate these processes, we use animal models and tissues from male and female patients undergoing cardiac surgery in the following objectives: 1) sex-specific role of ER? and ER? on mitochondrial energy production in the human heart; 2) sex-specific role of ER? and ER? effects in cardiac fibrosis; 3) role of mitochondrial cAMP-signaling in the cardioprotective effects of ER; 4) sex differences in calcium-dependent cardiomyocyte death in heart failure; 5) integrative model of sex differences in cardiomyocyte function and testing of targets.