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.