Anne-Marie Koop

1 15 Right ventricular metabolism RV pressure load is accompanied with metabolic derangements. 56–58 RVmetabolism may fulfil a central role in RVadaptation due to the interactionswith various processes of RV remodelling. 2,57,59,60 In the healthy adult heart, fatty acid metabolism is the primary source of energy (60-90%), whereas glucose metabolism is present in lesser extent (10-40%). 61 During RV stress a fetal switch takes place, which incorporates altered metabolism. 43,62–66 Metabolism during fetal life relies predominantly on the substrates glucose and lactate, due to substrate availability and a greater efficiency in a low oxygen environment. 43,67 As result of the reactivation of the fetal program in the stressed adult myocardium, the oxidative metabolism of fatty acids switches back to glucose metabolism with predominance of glycolysis, which has been associated with high proliferative processes in various organs and tissues. 68–70 Next to increased use of glucose and lactate, also ketones and amino acids serve as substrates in the stressed myocardium. 71 The role of fatty acid metabolism in the pressure loaded RV has been differently described in various models of RV pressure overload, and inhibition of fatty acid metabolism has been considered as a therapeutic option. 72–76 Therefore, we systematically reviewed glucose and fatty acid metabolism in the pressure loaded RV encompassing various models of increased RV pressure load in chapter 3 . In addition, in chapter 4 , we assessed the course of mitochondrial respiratory capacity in a model of fixed increased afterload over time. The roles of lipids in the RV, other than serving as a substrate, lipotoxic compound, anti-oxidant, or as part of the mitochondrial membrane, are sparsely studied. 77,78 We performed lipidomics to map alternations in intracardiac lipids in the pressure loaded RV in chapter 4 . Right ventricular molecular mechanisms Recent work indicates that transcription factors may be differently regulated in the RV compared to the LV. 66 This stems from the different embryonic origin of the two ventricles. Regulatory mechanism in right ventricular adaptation may be different regulated compared to left ventricular adaptation because the different embryonic origin of both ventricles. The heart is formed out of two types of progenitor cells representing the primary and secondary heart field. The primary heart field forms the LV and the atria, whereas the second heart field forms the RV, the outflow tract and the atria. 79,80 Genetic transcription in the myocardium is regulated by transcription factors. Where some factors can be found in both heart fields, other transcription Pressure load induces metabolic shifts associated with high proliferative processes.