Anne-Marie Koop

16 factors are heart field specific. In fetal development of the heart, certain transcription factors are essential for RV development, i.e. islet 1, Nkx-2.5, GATA4, -5 or -6, and the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2). 79,81–85 Deletion of these genes will be lethal or induce severe RV pathology. 86 On the other hand, some of these transcription factors contribute to pathologic remodelling in the stressed adult LV. 87 This raises the questionwhat the role will be in the stressed adult RV. In the current thesis ( chapter 7 ), we studied the role of Hand2 in the pressure loaded RV. Next to transcriptional activation, gene expression is also regulated at post-transcriptional level. In general, non-coding microRNA’s (miR’s) are progressively studied. 88–90 Studies in cardiac tissue showventricular specific assessments expression levels of miR’s. 91 However, the role of many of these miR’s in the stressed RV still needs to be unravelled. This emphasizes the different origin of both ventricles and hereby the relevance of research clarifying the RV specific factors during post-fetal life in order to develop therapy targeting RV disease. In chapter 6 we studied the role of miR-199b in the pressure loaded RV. SCOPE OF THE THESIS The general aim of this thesis was to investigate RV adaptation due to increased pressure load, at both molecular and functional level. Hereby, we specifically focused on RV metabolism and we tested whether previous identified molecular mechanisms of ventricular remodelling in the LV also apply to the RV. OUTLINE OF THE THESIS • Chapter_2_ Here we characterized a rat model of chronic pressure overload induced by pulmonary artery banding at different time points (at five weeks and time of termination) and disease severity (RV dysfunction versus clinical RV failure). In this model we assessed RV function by echocardiography and right heart catheterization, and molecular changes using RT-PCR, histological techniques and microarray analysis. • Chapter_3_ In this chapter we describe metabolism in the pressure loaded RV by providing an overview of current available literature, specifically focusing on glucose and fatty acid metabolism. In this systematic review and meta-analysis both animal experiments and clinical studies were included. • Chapter_4_ Temporal changes of RV function, remodelling and metabolism at two, five and twelve weeks were assessed in a rat model of RV pressure load. Furthermore, we performed lipidomics to assess the effect of pressure overload on the RV lipid content.