J Clin Invest.
Mitochondrial ROS increases ox-CaMKII and SAN cell death.
(A–C) SAN staining from WT mice treated with STZ alone and MitoTEMPO and STZ and Ncf1–/– mice treated with STZ. DAPI (blue) marks nuclei, HCN4 (green) marks SAN. Scale bars: 50 μm. (A) Representative sections show ox-CaMKII expression. Overall P = 0.006, **P < 0.01 by 1-way ANOVA (n = 3–5 per group). (B) Representative sections show TUNEL-positive cells. Overall P = 0.0006, ***P < 0.01 by 1-way ANOVA (n = 3–7 per group). (C) Fibrosis measured by Masson’s trichrome staining. Overall P = 0.016, *P < 0.05 by 1-way ANOVA (n = 3–4 per group). (D) Proposed model for CaMKII activation by STZ-induced diabetes. STZ-induced hyperglycemia and MI promote mitochondrial ROS generation, which activates ox-CaMKII to cause SND, leading to increased mortality after MI.