Figure 6. Loss of UCP2 reduce adult CM cell cycle activity in response to hypoxia.
(A–C) Cell cycle activity is significantly reduced in mice lacking UCP2 under hypoxia compared with their WT littermates, as evidenced by decreased levels of Ki67 (A), EdU incorporation (B), and pHH3 (C) 4 weeks after moderate hypoxia. Ki67, EdU, pHH3, green; α sarcomeric actin, red; nuclei, blue. Images taken in Z stack. Scale bar: 40 μm (n = 10). (D) Representative immunostaining image for wheat germ agglutinin (WGA). WGA, yellow; PCM1, red; nuclei, blue. Scale bar: 40 μm. (E) Cell size quantification from WGA images showing increased cardiomyocyte size in mice lacking UCP2 (n = 10). (F) Heart/body weight ratio is increased in UCP2KO mice under hypoxia compared to their littermates (n = 10 animals per group). (G) Quantification of ploidy levels in PCM1+ CM nuclei in WGA-stained images. (H) Quantification of the number of nuclei per cardiomyocytes in WGA-stained images showing decreased mononucleated and increased bi- and multinucleated cardiomyocytes in mice lacking UCP2 under hypoxia (n = 6). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data from A–C, F, and H were analyzed using Kruskal-Wallis test with Dunn’s correction for multiple comparisons; for E and G, 1-way ANOVA with Bonferroni post hoc test for multiple comparisons was applied.