FIGURE 7.

Ivabradine, but not zatebradine, ameliorates the diabetes-induced increases in fibrogenic protein expression and fibrosis (A) Collagen I, collagen III, TIMP2, and MMP2 protein expression was determined by western blotting in left ventricular fibroblasts isolated from mice administered ivabradine at the indicated doses (B) Left ventricular fibroblasts were isolated from mice administered zatebradine at the indicated doses and the expression of the proteins listed in (A) was measured by western blotting (C and D) Mice were treated as described in (A) and (B) and the degree of cardiac fibrosis was determined by Massonʼs trichrome staining and immunohistochemistry. The columns show the differences in collagen accumulation (original magnification ×400). Scale bars, 50 μm. Data in (A–B) (n = 3) and (C–D) (n = 6) are presented as mean ± SEM. p-values were calculated using one-way ANOVA with Tukey multiple comparison test. *p < 0.05, compared to the Control group; ^# p < 0.05, compared to the db/db mouse group.