3.2 LCZ696 treatment and TLR2 deficiency alleviated
doxorubicin-induced cardiac fibrosis.
Next, we assessed fibrosis in the heart tissues. Masson’s trichrome and
Sirius Red stains were chosen to evaluate connective tissue and
collagen, respectively, and validated the anti-fibrotic effects of
LCZ696 and TLR2 deficiency. As shown in Figure 2A-C, DOX promoted
collagen deposition in myocardial tissue, and these histological changes
were obviously improved in LCZ696-treated and TLR2-deficient mice.
In addition to the histological results, the hearts from DOX-challenged
mice showed significantly increased mRNA levels of the profibrotic genesCol1a (Figure 2D) and Tgfb (Figure 2E), which were notably
reduced by LCZ696 and TLR2 deficiency. These results paralleled the
protein levels of collagen I and TGF-β in the hearts of each group
(Figure 2F and Supplementary Figure 1A-B).
These results demonstrated that LCZ696 treatment and TLR2 deficiency
reduced doxorubicin-induced cardiac fibrosis.