Fig. 4: APOE overexpression rescues A/A mice from acute stress-induced cardiac electrophysiological abnormalities. | Nature Communications

Fig. 4: APOE overexpression rescues A/A mice from acute stress-induced cardiac electrophysiological abnormalities.

From: Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease

Fig. 4

a Continuous injection of E induced APOE expression in WT and A/WT mice, but not in A/A mice (n = 3). b AAV9-mediated APOE overexpression rescues cardiomyocyte damage in A/A mice induced by continuous E injection. AAV9-cTnT-Ctrl (AAV-Ctrl) or AAV9-cTnT-HA-tagged-APOE (AAV-APOE, 3 × 1011 viral genomes in 100 μl saline) was administered at 4 weeks of age. After 4 weeks, the mice received epinephrine (1 mg/kg/day) or saline for 3 days. Evans blue dye (EBD) uptake (left) and corresponding damage quantification (right) (n = 5). Scale bars, 50 μm. One-way ANOVA with Tukey’s posttest. c AAV9-mediated APOE overexpression decreased Tn-I levels in A/A mice induced by continuous E injection. The treatment of mice as in (b), (n = 5), One-way ANOVA with Tukey’s posttest. d AAV9-mediated APOE overexpression rescued A/A mice from acute stress-induced cardiac electrophysiological abnormalities. ECG was recorded before and 1 or 3 days after E injection (1 mg/kg/day), with/without APOE overexpression (n = 4), The treatment of mice as in (b). e Action potential duration at 90% repolarization (APD90) was measured in cardiomyocytes derived from A/A mice. The treatment of mice as in (b). (AAV-Ctrl, n = 22 cells; E + AAV-Ctrl, n = 13 cells; E + AAV-APOE, n = 25 cells; 3 mice per group). One-way ANOVA with Tukey’s posttest. f MitoSOX staining was performed on frozen heart sections in A/A mice to detect mitochondrial superoxide. The treatment of mice as in (b). Representative images were shown (n = 5). Scale bars, 30 μm. g TMRM staining of mitochondrial membrane potential in isolated cardiomyocytes from WT and A/A mice after 3 days of epinephrine (1 mg/kg/day) or saline (n = 5). Two-way ANOVA with Bonferroni post hoc correction. h TMRM staining of mitochondrial membrane potential in A/A mice cardiomyocytes after 3 days of epinephrine or saline injection (1 mg/kg/day), with/without APOE overexpression (n = 5). One-way ANOVA with Bonferroni post hoc correction. Data were shown as mean ± SD (b, c, e, g, h) from three to six independent experiments.

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