Fig. 5
From: RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome
Efficacy of anti-histone aptamers when administered after histones. a Aptamer inhibition of histone-mediated cytotoxicity of endothelial cells determined by MTS assay. EA.hy926 cells treated with 200 µg mL−1 of calf thymus histones followed by administration of either vehicle (negative control), heparin (positive control, 1:1), KU7 aptamer (1:2) or KU9 aptamer (1:2) at time points of 0, 5, 10, 15, 30, 45, 60, 90, 120 and 180 min after CTH; n = 3 biological replicates; *p < 0.0025 vs. vehicle. b Dynamic changes of intracellular calcium levels in Fura 2-AM-loaded EA.hy926 cells using fluorescence microscopy. (Left panel) Representative intracellular calcium elevation traces (F340/F380) of EA.hy926 treated with CTH (50 µg mL−1) then followed by addition of vehicle or aptamer KU7 (Molar ratio of CTH to aptamer 2:1) added 1 min after CTH. (Right panel) Summary of data (*p < 0.0001 vs. CTH, unpaired two-tailed t-test, n = 23–27 cells). c Efficacy of anti-histone aptamers in murine model of MODS. Survival curves of mice injected IV with vehicle, or CTH (62.5 mg kg−1), followed in 30 min by IV injection of vehicle or aptamer KU9 (31.25 mg kg−1, indicated as 2nd injection); n = 6 biological replicates; *p < 0.05 vs. CTH+vehicle. Lung weight normalized to pre-treatment body weight. *p < 0.05 vs. Veh, one-way ANOVA corrected for multiple comparisons (Dunnett testing), n = 3–5 per group, data represent mean ± SEM
