Merging Macro and Micro: Transcriptional landscapes and in-depth studies for understanding heart disease

Abstract

Various heart diseases can progress to heart failure in the long term. Heart failure is defined as a clinical syndrome caused by structural and/or functional abnormalities of the heart resulting in increased intracardiac pressure and/or insufficient cardiac output. Due to the relative high prevalence, heart failure has an enormous burden on society, ranging from an individual’s perspective to a macro-socioeconomic standpoint. This thesis describes studies that use a modern technique called single-cell RNA sequencing to study heart failure. With this technique, detailed molecular changes in heart failure can be examined. By subsequently studying a single molecular change in detail, insight can be gained into whether this is a potential target for new drugs. Accurately mapping these detailed molecular changes can thus be a source for potential new therapies. In this dissertation, we look at the molecular changes in different causes of heart failure in animal models and combine this with data from patients and cell culture experiments. Additionally, we identify a previously relatively unknown protein (SORBS2) and describe the importance of this protein in heart failure. The results of this dissertation contribute to an improved understanding of heart failure.