Heart failure as a result of myocardial infarction and ischaemic heart disease remains the most prominent health challenge of the developed world, with a five year survival rate of less than 50%. Although, many breakthroughs have been made, the fundamental mechanisms responsible for the development and progression of heart failure have not yet been fully elucidated. In recent years it has been observed that cardiac injury in the adult heart leads to a switch in gene expression which to some extend resembles the expression pattern observed in the fetal heart, a process dubbed cardiac fetal reprogramming. With this thesis we tried to further characterize cardiac fetal reprogramming in heart failure, and how a better understanding of this process can lead to novel therapeutic strategies for patients. We identified OPLAH as a novel cardiac fetal gene, which has encodes for an enzyme that has a cardio-protective effect in heart failure. Additionally we demonstrated that 5-oxoproline, substrate of OPLAH, levels are elevated in plasma of heart failure patients, suggesting this metabolite to be a novel putative biomarker in patients with heart failure. Together these findings identify OPLAH and 5-oxoproline as a novel pathophysiological pathway in heart failure, and targeting the expression and/or activity of OPLAH may lead to new therapeutic options of heart failure patients.
|Translated title of the contribution||Cardiale foetale gen programma in hartfalen|
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2018|