3.6 Administration of LCZ696 attenuated
doxorubicin-induced cardiac injury by inhibiting TLR2-MyD88 complex
formation.
To explore the underlying mechanism of the effect of LCZ696 and TLR2
deficiency on DOX-related cardiac injury, TLR2-MyD88 complex formation
and the well-established TLR2 downstream pathway were analyzed.
First, H9C2 cells were treated
with DOX in a time-dependent manner. The Co-IP assay results showed that
DOX significantly increased the TLR2-MyD88 interaction in 15 mins
(Figure 6A), which indicated the potential mechanism of TLR2-mediated
DOX-related cardiomyopathy. More interestingly, DOX-induced TLR2-MyD88
complex formation was attenuated by pretreatment with LCZ696 (Figure
6B). These results indicated that the treatment effect of LCZ696
manifests by inhibiting TLR2-MyD88 complex formation induced by DOX.
Furthermore, we found that the TLR2-MyD88 complex formation induced by
DOX was independent of TLR4 and MD2, as it was not affected by TLR4 or
MD2 knockdown (Figure 6C-D, Figure 7).