Anne-Marie Koop

3 91 The etiology of disease, or the character of the model, is important since models of PAH, as hypoxia, SuHx, MCT and FHR, may differ in their systemic effects and are known for differences in disease severity and cardiovascular interaction. These differences are driven by involvement of endothelial damage, level of inflammation, cytokine migration and vasoconstriction. While isolated hypoxia with the absence of endothelial damage in the pulmonary vasculature induces mild PH only, FHR leads to more progressive PH, whereas SuHx and MCT will induce failure, with high rates of mortality in MCT. Exact mechanisms still need to be unraveled. The current meta-analysis directs to further exploration of the role of diseases which expose the RV to altered insulin sensitivity or oxygen tension in remodelling during RV pressure load. Current overview shows that determination of protein expression is limited compared to gene expression, and often shows divergent results. Also, measurements of substrate activities are relatively scarce. We suggest future studies in the pressure loaded RV should be more uniform and integral with respect to expression level (gene, protein , or activity level). The to be studied variables of metabolism should be uniform and most optimal chosen based on research using unbiased approaches (i.e. microarray, RNAsequences, proteomics ormetabolomics). Given the above mentioned observations, the translational applicability between, and within, animal models and human diseases of PH should most critically and carefully be considered. CONCLUSION This systematic review and meta-analysis of metabolic variables in the pressure loaded RV showed uniform increase in glucose uptake and glycolysis. Results regarding fatty acid uptake and changes in oxidativemetabolismwere divergent and model specific. To actually use metabolism as therapeutic target in the RV exposed to increased pressure load in clinical practice, we need to learn more about model and disease specific mechanisms of fatty acid uptake and mitochondrial impairment. SOURCE OF FUNDING Not applicable. DISCLOSURES None.