Fig. 7: Tyrosine kinase receptor inhibitor AG-825 reduces cardiac myocyte disarray without effects on contractile function in TgErbB2 mice.

a Masson’s trichrome stained sections (5X) from vehicle-treated Ntg and AG-825–treated Ntg and vehicle-treated TgErbB2 and AG-825-treated TgErbB2 mice, yellow arrowheads point to fibrotic areas. Scale bar 1 mm. b Masson’s trichrome stained sections (40X) from representative regions of interest show increased Fibrosis in TgErbB2 mice myocardium, that fibrosis improved after 2 weeks of AG-825 Treatment. The same areas were used to determine the level of cardiac myocyte disarray, which was achieved by analyzing cell orientation using CytoSpectre Software from Vehicle and AG-825 treated Ntg and TgErbB2 mouse heart sections (scale bar 50 μm). c Plots of the distribution of cardiac cells orientation angles. Note how Ntg angles are homogeneous and did not change in the group treated with AG-825. In contrast, Tg treated with vehicle showed less homogenous and different orientation angles, confirming cardiomyocyte disarray. AG-825 Treatment reduces cardiomyocyte disarray, and the orientation plot is similar to the AG-825 treated NTG group. d Mean orientation angle of cardiac myocytes, and e Circular variance, another measure of isotropy, in Ntg and TgErbB2 mice with and without AG-825 treatment (n =  5 animals per condition). Graph bars are expressed as mean ± s.e.m.; a one-way ANOVA test was performed for statistical comparisons showing a significant improvement in TgErbB2 mice treated with AG-825 (p-value < 0.0014). f Cardiac echocardiography from the four groups shows that AG-825 Treatment for 14 days did not modify the contractile function, estimated as % Fraction Shortening.