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. 2017 Apr 24;8:15104. doi: 10.1038/ncomms15104

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Copyright © 2017, The Author(s)

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(a,b) Echocardiographic images (a) and cardiac function (b) of Xrcc1^f/f, Xrcc1^αMHC-Cre and Xrcc1^αMHC-Cre; Atm^+/− mice. Statistical significance was determined by one-way analysis of variance (ANOVA) followed by the Tukey-Kramer HSD test. **P<0.01 between arbitrary two groups. (c) The type of DNA damage in cardiomyocytes of Xrcc1^f/f, Xrcc1^αMHC-Cre and Xrcc1^αMHC-Cre; Atm^+/− mice was assessed by comet assay (Alkaline comet: n=50, 76, 77; Neutral comet: n=53, 56, 42, respectively). Statistical significance was determined by Steel-Dwass test. (d,e) Activation of DDR in Xrcc1^f/f, Xrcc1^αMHC-Cre and Xrcc1^αMHC-Cre; Atm^+/− mice was assessed by immunostaining for phosphorylated H2AX (d, γH2AX, green, arrowheads). Immunostaining for alpha-actinin (red) was used to label cardiomyocytes. Arrowheads indicate γH2AX-positive cardiomyocytes. Scale bar, 50 μm. The number of γH2AX-positive cardiomyocytes was counted (e, n=4 each). Statistical significance was determined by one-way ANOVA followed by the Tukey-Kramer HSD test. *P<0.05 between arbitrary two groups. (f) The expression levels of inflammatory cytokines in the isolated cardiomyocytes of Xrcc1^f/f, Xrcc1^αMHC-Cre and Xrcc1^αMHC-Cre; Atm^+/− mice was assessed by real-time PCR (n=7, 7, 6 for each genotype, respectively, technical duplicates). Statistical significance was determined by one-way ANOVA followed by the Tukey–Kramer HSD test. *P<0.05 between arbitrary two groups. (g,h) Heart tissues of Xrcc1^f/f, Xrcc1^αMHC-Cre and Xrcc1^αMHC-Cre; Atm^+/− mice were immunostained for CD45 or CD68 (g, green, arrowheads). Immunostaining for alpha-actinin (red) was used to label cardiomyocytes. Arrowheads indicate CD45- or CD68-positive cells. Scale bar, 50 μm. The number of CD45- and CD68-positive cells was counted (h, n=6, 6, 4 for each genotype, respectively). Statistical significance was determined by one-way ANOVA followed by the Tukey–Kramer HSD test. **P<0.01 between arbitrary two groups. Column and error bars show mean and s.e.m., respectively. LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension; LVPWd, left ventricular posterior wall dimension; LVFS, left ventricular fractional shortening (n=83, 88, 23 for each genotype, respectively).