Figure 4: Biochemical and Molecular Effects of UCn2 and UCn3 Gene Transfer on LV Samples

LV transmural samples obtained 9.0 ± 0.2 weeks after IV delivery of AAV8.UCn2 or AAV8.UCn3 (both at 1.9 × 1013 gc/kg), or saline (control). (A) Basal cAMP production showed no group differences. (B) Basal PKA activity showed no group differences. (C) Phosphorylated CaMKIIα-Thr286 protein levels showed group differences: UCn2 and UCn3 gene transfer reduced CaMKIIα phosphorylation to similar degrees. (D) Phosphorylated ryanodine receptor 2 protein levels showed group differences, solely attributable to reduction conferred by UCn2 gene transfer (p = 0.01 vs. UCn3, Dunn’s multiple comparison test with correction). (E) LV SERCA2a protein levels were increased similarly by UCn2 and UCn3 gene transfer. Individual data are shown (mean ± SE); p values are from Kruskal-Wallis test. Abbreviations as in Figure 1.