Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model
Fig 9
Myh14 deficiency under ISO results in LVM hypertrophy, LVIDd dilation, increased cardiomyocyte size, fibrosis, intercalated disc disarray, and hypertrophic signals.
Female mice of wild-type (WT), heterozygous (HET) and knockout (KO) Myh14 genotypes were treated with ISO at 10–12 weeks of age (n = 6, 9, and 7, respectively). Myh14 deficiency conferred an increase in ISO-induced LVM hypertrophy (A) and LVID dilation (B). There was a trend towards decreased ISO-induced EF (C) due to Myh14 deficiency. Cardiomyocyte cross-sectional area, as measured by wheat germ agglutinin (WGA) staining (D), showed that cardiomyocytes from ISO-treated KO mice were more significantly hypertrophied compared to HET and WT mice (E). Dark gray bars (baseline in A and B; average of baseline and week 1 in C; control in E). Light gray bars (average of weeks 1–3 measures in A and B; average of weeks 2–3 measures in C; ISO-treated in E). Myh14 deficiency conferred an increase in ISO-induced fibrosis (blue arrow) by Masson’s trichrome staining (F) and an increase in intercalated disc disarray (blue arrow) by β-catenin staining (G). Cardiac tissue gene expression of hypertrophic and fibrosis markers were examined by RT-PCR at the end of a 3-week ISO infusion (H). Myc, Nppb, and Lgals3 were increased with Myh14 deficiency. Error bars are SEM, n = 3. * represents t-test p-value < 0.05. ** represents t-test p-value < 0.005.