Inhibition of mTORC1 renders cardiac protection against lipopolysaccharide.

Abstract

Sepsis-induced cardiac dysfunction is a severe clinical problem. It is evident that rapamycin can protect heart from pathological injuries. However, there are no data demonstrating rapamycin reverse cardiac dysfunction induced by sepsis. In this study, Lipopolysaccharide (LPS) was administrated to mice and H9c2 cells. After treatment, we further determined cardiac function by echocardiography, ANP, BNP and inflammatory markers by qPCR and apoptosis by TUNEL staining. Moreover, mTORC1 signaling pathway and Akt activity were measured by Western blots. We found that rapamycin attenuated cardiac dysfunction, increase in ANP and BNP as well as apoptosis induced by LPS both in mice and in H9c2 cells. Unexpectedly, LPS did not significantly affect the mRNA levels of TNF-α and IL-6. Furthermore, rapamycin further reduced the decrease in mTORC1 signaling and Akt activity induced by LPS. In conclusion, rapamycin can protect heart from LPS induced damages by inhibition mTORC1 signaling and elevation of Akt activity.