title: 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.
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China ; Department of Pathology, Gansu Provincial Hospital Lanzhou 730000, Gansu, People's Republic of China.
authors: Xiang
authors: X
authors: Li
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Lijing
authors: L
authors: Jiang
authors: Department of Cardiology, Jinjiang Hospital of Quanzhou Medical College Jinjiang 362200, Fujian, People's Republic of China.
authors: Shenghui
authors: S
authors: Lin
authors: Minhang District Maternal and Child Health Hospital of Shanghai Minhang, Shanghai 201199, People's Republic of China.
authors: Yunfen
authors: Y
authors: He
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Guofeng
authors: G
authors: Shen
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Zhenlin
authors: Z
authors: Cai
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Meirong
authors: M
authors: Ling
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Jindi
authors: J
authors: Ni
authors: Department of ICU, Minhang Hospital, Fudan University Minhang, Shanghai 201199, People's Republic of China.
authors: Hao
authors: H
authors: Zhang
authors: Department of Pathology, Gansu Provincial Hospital Lanzhou 730000, Gansu, People's Republic of China.
authors: Min
authors: M
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000633:toxicity; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: LPS; cardiac dysfunction; mTORC1; rapamycin