EstroHeart. Understanding the Female Heart Health, Aging Mechanisms and Sex Differences

Heart disease is a global health issue, affecting 56 million people worldwide. Interestingly, half of these individuals are women. Women tend to experience more severe side effects from heart medications, live longer, and face a higher risk of heart disease as they age. Despite these facts, women are often underrepresented in heart disease research. To address this gap, we will investigate the female heart and how it changes with age. We will focus on key areas such as heart muscle growth (hypertrophy), tissue scarring (fibrosis), inflammation, and the role of estrogen. We will use advanced molecular biology techniques to study these aspects. To understand the differences between men and women, we will compare our findings with data from aging male hearts. Since it's challenging to get heart tissue from healthy and aging humans, we will use rats and mice as model systems. Additionally, we will investigate if human stem cell-derived heart cells can be used to study sex-specific mechanisms. The relevance of our findings will be tested on human heart tissue. This research is expected to provide new insights into the female heart and its aging process. In the long run, this knowledge might lead to the development of better heart medications tailored specifically for women, improving their health and quality of life.

Heart disease affects 56 million people worldwide, with half of them being women. Women experience more adverse side effects from medications, live longer, and are at greater risk of cardiac disease in the second half of their lives. Despite this, women are underrepresented in most cardiac research studies. To advance in cardiac research, there is a need to acquire deeper knowledge of the female heart and alterations during cardiac aging. In the proposed project, we will investigate the female heart and cardiac aging, with a focus on hypertrophy, fibrosis, inflammation, and estrogen signaling networks, using different approaches, including OMICs analysis. To reveal sex-specific differences, the data will be compared with aging male data. In our preclinical design, we will use rats and mice as model systems considering the difficulties of obtaining cardiac tissue from healthy and aging humans. We will also investigate whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used as a model system for studying sex-specific mechanisms. Translational relevance will be assessed in human cardiac tissue. New knowledge on the female heart and cardiac aging is expected to advance the state of the art and open new research lines, particularly in female aging cardiology. In the long term, this new knowledge can be exploited in the design of the next generation of female and sex-specific cardiac drugs with improved therapeutic effects, saving patients' lives and improving their quality of life. We will employ aging rats, genetically modified mice, hiPSC-CMs and human cardiac tissue from both sexes, magnetic resonance imaging, echocardiography, single cell RNA-sequencing, proteomics, bioinformatics, cardiomyocytes, high-resolution imaging, cyclic stretch, peptide array and adendo-associated virus technology, and a plethora of other molecular biology methods. The project has both national and international collaborators.