Figure 6.

Expression analysis of remodeling processes in cardiac tissue of CVB3-infected C57BL/6J mice 7 and 28 days after infection. (a) Gene expression analysis in cardiac tissue of healthy (white bar) and CVB3-infected C57BL/6J mice 7 days p.i. (light grey bar) as well as 28 days p.i. (dark-grey bar) was determined using TaqMan analysis. The mRNA expression of profibrotic genes Col1a1, Col3a1, and Ctgf was increased in mice 7 days after CVB3 infection and dropped down to normal expression levels 28 days after infection. Furthermore, expression of genes involved in the regulation of ECM degradation was increased within 7 days after infection. Timp1, the endogenous inhibitors for MMPs, as well as the collagenase Mmp13 was significantly upregulated in cardiac tissue 7 days after infection. Since the Timp1 expression raised more than the Mmp13 expression the ratio Timp1/Mmp13 revealed an increased Mmp13 inhibition. Data are presented as absolute mRNA expression (x-fold to the house keeping gene 18S) in box plots as well as in fold change to control animals as mean ± SEM above the corresponding bar using the formula 2^−ΔΔCt. (b) Detailed histological stainings were performed to quantify cardiac remodeling and plotted as area fraction of healthy (white bar) and infected C57BL/6J mice 7 days p.i. (light grey bar) and 28 days p.i. (dark-grey bar). Tissue sections were stained for COL-I as well as COL-III. COL-I staining of cardiac tissue yielded in a significant increase of fibrosis in CVB3-infected mice 7 days after infection compared to healthy controls. Analyses of COL-III did not show significant changes in cardiac tissue after CVB3 infection; ^∗significantly different compared to noninfected mice (control); ^∗P < 0.05; ^∗∗P < 0.01; ^∗∗∗P < 0.001; ^∗∗∗∗P < 0.0001; ^§significantly different compared to 7 days p.i.; ^§P < 0.05; ^§§P < 0.01; ^§§§P < 0.001;  ^nsnot  significant.