Min Luo, Xiaoqun Guan, Elizabeth D. Luczak, Di Lang, William Kutschke, Zhan Gao, Jinying Yang, Patric Glynn, Samuel Sossalla, Paari D. Swaminathan, Robert M. Weiss, Baoli Yang, Adam G. Rokita, Lars S. Maier, Igor R. Efimov, Thomas J. Hund, Mark E. Anderson
Oxidation-resistant CaMKII and myocardial CaMKII inhibition protects against SAN cell death and fibrosis.
(A) Representative immunoblots and Coomassie-stained gels from right atria of STZ-treated MM-VV and WT mice. CaMKII (**P = 0.001), ox-CaMKII (***P ≤ 0.001), and ox-CaMKII/CaMKII (*P = 0.002) in MM-VV (n = 5) and WT STZ-treated mice (n = 4). (B) Representative immunofluorescence images of SAN from MM-VV and WT STZ-treated mice. Scale bars: 50 μm. CaMKII (P = 0.09) and ox-CaMKII (*P = 0.02) in MM-VV (n = 4) and WT STZ-treated mice (n = 5). HCN4 (green) marks SAN, and DAPI (blue) marks nuclei. (C) Representative SAN sections show TUNEL-positive staining (72) in WT mice after vehicle or STZ treatment and in MM-VV and AC3-I mice after STZ treatment. DAPI (blue) marks nuclei, HCN4 (green) marks SAN. Scale bars: 50 μm. Overall P < 0.0001, ***P < 0.001 by 1-way ANOVA (n = 3–5 per group). (D) Caspase-3 activity in SAN from WT mice after vehicle or STZ treatment and in MM-VV and AC3-I mice after STZ treatment. Overall P = 0.007, *P < 0.05, **P < 0.01 by 1-way ANOVA (n = 3 per group). (E) Representative Masson’s trichrome staining for fibrosis in SAN from STZ-treated WT, MM-VV, and AC3-I mice. Scale bars: 20 μm. Overall P = 0.005, **P < 0.01, ***P < 0.001 by 1-way ANOVA (n = 3–4 per group).