3.1 LCZ696 treatment and TLR2 deficiency attenuated doxorubicin-induced cardiac systolic dysfunction.
First, our objective was to determine whether LCZ696 and TLR2 deficiency inhibits doxorubicin-induced cardiotoxicity in mice. As previously reported, doxorubicin was used to establish chronic cardiac injury in mice through intraperitoneal injection. Then, LCZ696 was administered orally to determine whether it can prevent heart injury, and a model of doxorubicin-induced cardiac injury was also established in TLR2KO mice to explore the potential role of TLR2.
Before sacrifice, the cardiac function of each mouse was evaluated by external echocardiography (Figure 1A and Table 1). As shown in Figure 1A and Table 1, DOX significantly impaired heart function by decreasing EF%, FS%, IVSD, and PWd and increasing LVIDd, which resulted in serious systolic dysfunction. Interestingly, these challenges were normalized with oral LCZ696 treatment and TLR2 deficiency, which indicated that LCZ696 and TLR2 deficiency attenuated DOX-induced cardiac systolic dysfunction in mice.
To deeply explore the alterations of the heart cavity, histological assessments of the whole heart were performed for all groups by H&E staining. As shown in Figure 1B, DOX induced thinning of the ventricular wall and enlargement of the heart cavity, which were obviously improved in the hearts of LCZ696-treated and TLR2-deficient mice. The above results show that treatment with LCZ696 and TLR2 deficiency prevents DOX-induced cardiac systolic dysfunction.