Abnormal loading of the heart leads to the deterioration of heart function. For decades, clinical care and research focused on the left ventricle (LV), while knowledge about the right ventricle (RV) was left behind. This thesis describes (the regulation of) energy and remodeling processes of the abnormally loaded RV using studies in animal models and patients. We show that RV failure is associated with lack of relaxation of the heart muscle and reduced expression of genes involved in glycolysis (anaerobic metabolism of sugar), while meta-analysis shows that pressure load itself leads to increased RV sugar uptake and glycolysis. We were the first to identify that polyunsaturated fatty acids, especially cardiolipins, decrease in the pressure loaded RV. Cardiolipin is essential for adequate oxidative metabolism. However, oxidative metabolism was not yet affected at this point. Identifying the lipid profile may enable early identification of RV disease. This thesis also investigated whether previously identified regulatory processes in LV hypertrophy (enlarged heart muscle cells) also apply to the RV. This is not the case, which means that identified processes in the LV must also be investigated in the RV. Interestingly, in the LV itself these processes were affected in conditions of RV pressure load. Finally, we related biomarkers with type and degree of RV load, and RV remodeling and function in early stages of RV-disease. In conclusion, this thesis increases the knowledge of the abnormally loaded RV, which will support the development of tailored therapies.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||25-nov-2020|
|Status||Published - 2020|