Fig. 5: APOE overexpression rescues A/A mice from chronic stress-induced cardiac fibrosis and contractile dysfunction.

a TANNylated-Pep8 (TA-Pep8) reduced stress-induced cardiac fibrosis in A/A mice. The mice were intraperitoneally injected with epinephrine (E) or saline (S), subjected to SI or GH, and then injected intravenously with TA-Pep8 or TA-Pep8-S. Representative images of Masson’s trichrome-stained heart sections are shown at the left and quantification of the fibrosis area was shown at the right (n = 6). Scale bars, 50 μm, two-way ANOVA with Tukey’s posttest. b AAV9-mediated APOE overexpression mitigated stress-induced cardiac fibrosis in A/A mice. Negative control AAV9-cTnT-Ctrl (AAV-Ctrl) or AAV9-cTnT-HA-tagged-APOE (AAV-APOE, 3 × 10¹¹ viral genomes in 100 μl saline) was administered by intrathoracic injection at 4 weeks of age. After 4 weeks, the mice were exposed to E + SI or S + GH, and heart tissue samples were collected three weeks later. Representative images of Masson’s trichrome-stained heart sections are shown at the left and quantification of the fibrosis area was shown at the right (n = 6). Scale bars, 50 μm, two-way ANOVA with Tukey’s posttest. c, d AAV9-mediated APOE overexpression rescued A/A mice from stress-induced contractile dysfunction. The left ventricular ejection fraction (LVEF) (c) and left ventricular fractional shortening (LVFS) (d) were analyzed at baseline and 21 days of SI post E, with or without APOE overexpression as indicated. The treatment of mice was as described in (b), (n = 4), two-way ANOVA with Bonferroni post hoc correction for multiple comparisons. e MitoSOX staining was performed on frozen heart sections in A/A mice. The treatment of mice was as described in (b). Representative images of the MitoSOX-stained heart sections were shown (n = 5). Scale bars, 30 μm. f WB analysis was conducted to verify HA-tagged APOE expression for (e) (n = 3). Data were shown as mean ± SD (a–d) from four to six independent experiments.