Role of the mTOR Signalling Pathway in Human Sepsis-Induced Myocardial Dysfunction.

Published on Jul 1, 2019in Canadian Journal of Cardiology5.59
· DOI :10.1016/j.cjca.2019.03.022
Wei Cheng Mm1
Estimated H-index: 1
(Peking Union Medical College Hospital),
Yun Long10
Estimated H-index: 10
(Peking Union Medical College Hospital)
+ 3 AuthorsNa Cui6
Estimated H-index: 6
(Peking Union Medical College Hospital)
Abstract Background Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication of sepsis. Mammalian target of rapamycin (mTOR) signalling pathway is significantly associated with SIMD in an animal model; however, there have been no clinical studies of the association in humans. Methods We enrolled 88 patients with sepsis who were admitted to the intensive care unit (ICU) between April 2017, and April 2018. Biochemical indexes, hemodynamic parameters, and bedside echocardiographic parameters were recorded. Serum levels of mTOR, phosphorylated ribosome S6 protein kinase (PS6K), microtubule-associated protein light chain 3 type II (LC3B), Bcl-2-interacting mediator of cell death (BIM), interleukin 6, interleukin 10, and interferon-γ were examined. Results Compared with non-SIMD patients, patients with SIMD had higher ICU and 28-day mortality, PS6K and BIM levels, but lower LC3B levels. Serum PS6K levels in patients with SIMD were significantly negatively and positively correlated with LC3B and BIM, respectively. Multivariate regression analysis revealed that PS6K concentration at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that a PS6K concentration cutoff of 42.43 pg/mL at ICU admission could predict the incidence of SIMD with a sensitivity and specificity of 91.7% and 96.2%, whereas a cutoff concentration of 41.17 pg/mL PS6K could predict 28-day mortality with a sensitivity and specificity of 83.3% and 54.3%, respectively. Conclusions Patients with sepsis and SIMD had higher ICU and 28-day mortality. Higher serum PS6K concentrations were significantly associated with SIMD incidence and 28-day mortality, suggesting that activation of the mTOR pathway may play a major role in SIMD.
  • References (22)
  • Citations (1)
28 CitationsSource
#1Wen Han (Peking Union Medical College Hospital)H-Index: 2
#2Hao Wang (Peking Union Medical College Hospital)H-Index: 7
Last.Dawei Liu (Peking Union Medical College Hospital)H-Index: 12
view all 6 authors...
4 CitationsSource
#1Gina CasselH-Index: 1
#2Jules C. BealH-Index: 5
Last.Chhavi KatyalH-Index: 5
view all 6 authors...
13 CitationsSource
#1Jie Zhang (UMMC: University of Mississippi Medical Center)H-Index: 1
#2Peng Zhao (SDU: Shandong University)H-Index: 1
Last.Ji Li (UMMC: University of Mississippi Medical Center)H-Index: 34
view all 8 authors...
10 CitationsSource
#1Dajun ZhaoH-Index: 2
#2Jian YangH-Index: 15
Last.Lifang YangH-Index: 4
view all 3 authors...
31 CitationsSource
#1Brian K. Kennedy (Buck Institute for Research on Aging)H-Index: 66
#2Dudley W. Lamming (UW: University of Wisconsin-Madison)H-Index: 34
177 CitationsSource
#1Mervyn Singer (UCL: University College London)H-Index: 69
#2Clifford S. Deutschman (The Feinstein Institute for Medical Research)H-Index: 34
Last.Derek C. Angus (University of Pittsburgh)H-Index: 96
view all 19 authors...
3,598 CitationsSource
57 CitationsSource
27 CitationsSource
#1Chih-Wen LinH-Index: 7
#2Steven LoH-Index: 8
Last.Ya-Ching HsiehH-Index: 5
view all 10 authors...
25 CitationsSource
Cited By1
#1Keith R. Walley (UBC: University of British Columbia)H-Index: 43