Anne-Marie Koop

168 RV pressure load effects on inflammation and oxidative stress To assess the effects of pressure load on inflammation and oxidative stress in the RV, we analyzed recruitment of cytokines (interleukines) and macrophages (CD68), activation of oxidative stress (NAPDH oxidases), oxidation protein products and anti-oxidative markers in RV tissue. Cardiac gene expression of inflammatory markers CD68. control 2w 5w 12w 0 2 4 6 CD68 mRNA level (fold change) # * * * control 2w 5w 12w 0 2 4 6 8 10 GDF-15 mRNA level (fold change) * * * control 2w 5w 12w 0 2 4 6 8 macrophage in ltration macrophages per 10.000 μ m 2 control 2w 5w 12w 0 1 2 3 NOX2 mRNA level (fold change) # * 2w 5w 12w 0 40 80 120 160 AOPP control 2w 5w 12w 0 20 40 60 80 AOPP in plasma control 2w 5w 12w 0 1 2 3 4 NOX4 mRNA level (fold change) # * # anti-oxidant capacity trolox equivalent capacity control 2w 5w 12w 0 500 1000 GDF-15 in plasma GDF-15 (pg/ml) A B C E G advancedoxidationprotein products (μM) I (nmol/mg) F H J D PAB control 2 weeks 5 weeks 12 weeks Figure 4 advancedoxidationprotein products (nmol/mg) a nt i-ox idan t capa ci 2w 5 w 12w 0 10 20 30 Figure 4. Inflammation and oxidative stress over time in RV pressure load. mRNA expression of macrophage marker CD68 (A), and GDF-15 (B) in RV tissue. Macrophage infiltration measured by CD68-staining (C), with representative images of histological analysis (ruler is 100 µm) (D). mRNA expression of NOX2 and NOX4 as activators of oxidative stress (E-F). AOPP as marker of actual oxidative stress (G) and anti-oxidant capacity assay (H) in RV tissue. Levels of AOPP and GDF-15 in blood-plasma (I-J). Data presented as mean±SEM. * = p < 0.05 compared to control, # = p < 0.05 compared to indicated time point. ● = individual animal, white = control group, grey = pulmonary artery banding groups. PAB = pulmonary artery banding. 2w, 5w and 12w = 2, 5 and 12 weeks after PAB. CD68 = cluster differation 68, GDF-15 = growth differation factor 15, NOX = NAPDH oxidase, AOPP = advanced oxidation protein products.