WNT5A Increases O2.– Generation in Human and Murine Myocardium
(A to D) Basal, NADPH-stimulated, and VAS2870-inhibtable O2.– production in human myocardium according to tertiles of WNT5A or FZD5 expression in myocardium (n = 189 in A to C; n = 181 in D). Data are presented as median (25th-75th percentile). ∗P < 0.05, ∗∗P < 0.01 by Kruskal-Wallis test; ††P < 0.01 vs low tertile by Dunn’s test corrected for multiple tests. (E to H) O2.– production and fold change of activated Rac1 in human myocardium in presence/absence of WNT5A and SFRP5 (n = 5). ∗P < 0.05 vs control by Wilcoxon signed paired rank test. (I) Breeding scheme for inducible expression of FLAG-tagged Wnt5a. (J) Doxycycline (DOX) treatment induces marked Wnt5a overexpression in Wnt5a+/rtTA+ hearts (n = 5). O2.– production (K to M) and Rac1 activation (N) in hearts of DOX-treated mice (n = 6-8 per group). Lines on scatterplots represent median values. ∗P <0.05, ∗∗P < 0.01 vs control by unpaired t test. Myoc = myocardial; PminCMV = promoter; RLU = relative light unit; rtTA = reverse tetracycline-controlled transactivator; TRE = tetracycline-response element; other abbreviations as in Figures 1 and 4.