Anne-Marie Koop

3 83 Oxidative fatty acid metabolism β -oxidation involved genes including ACADVL (1), EHHADH (2), HADHA (1), ACAA2 (3), ACAT1 (1), MCAD (synonym ACADM) (6), ACADS (3), ACOT2 (1) were all described, but only MCAD did meet the criteria for inclusion in meta-analysis. MCAD at mRNA level decreased in all models of RV pressure load (hypoxia p < 0.001, SuHx p < 0.01, and PAB p < 0.05) 5,27,34,35,46 ( figure 5e ). No correlations with duration or degree of pressure load were observed ( suppl. table 2 and 3 ). At protein level three studies 27,46,47 were included in meta-analysis, which tended to decrease, but did not reach statistically significance (g = -2.02, p = 0.141)( suppl. figure 3 ). Mitochondrial respiration regarding fatty acid oxidation measured in the ADP-driven state (n=4) decreased, when tested in models of hypoxia 29,42 and SuHx 20 ( figure 5f-1 ). Respiratory capacity in intact cardiomyocytes was extracted from two publications showing contrary results in PAB 21 compared to FHR-model 16 ( figure 5f-2 ). Transcriptional regulators of metabolism This systematic search identified several regulators of transcriptional regulators of metabolism, i.e. PGC1 α (5), PPAR α (4), PPAR γ (1), FOXO1 (1), Mef2c (1), HIF1α (4) and cMyc (1) (numbers include both gene expression at mRNA level and protein expression). Meta-analysis was performed for PGC1 α and PPAR α . PGC1 α is best known as the master regulator of mitochondrial biogenesis and interacts with PPAR α which predominantly acts on lipids metabolism. Combined Hedges’ g of PGC1 α mRNA expression 27,43 decreased ( suppl. figure 4b ) and meta-regression revealed a negative correlation with duration of pressure load ( suppl. figure 4c ). Meta-analysis for PGC1 α protein expression did not reveal significant change ( suppl. figure 4d ), but did show a model effect for MCT 43 vs. SuHx 20,27 (p < 0.05) ( suppl. figure 4b ). Combined Hedges’ g of PPAR α mRNA expression 27,34,35 during pressure load did not change significantly ( suppl. figure 4e ) and no correlations with duration, degree or model of RV pressure were observed. PPAR α protein expression was studied once in SuHx-rats, demonstrating a decrease (p < 0.001). 27 Results are summarized in figure 6 and supplemental table 4 . Oxidative metabolism in the pressure loaded right ventricle has been studied in various models, showing ambivalent results for both glucose and fatty acid metabolism.