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.