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Updated: Jan 22, 2026
Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis
Published on: June 14, 2024
Role of the mTOR Signalling Pathway in Human Sepsis-Induced Myocardial Dysfunction
Wei Cheng Mm1, Yun Long1, Hao Wang1
1Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
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.
Insights
Sepsis-induced myocardial dysfunction (SIMD) is linked to higher mortality. Elevated phosphorylated ribosome S6 protein kinase (PS6K) levels predict SIMD and mortality, suggesting the mammalian target of rapamycin (mTOR) pathway
Area of Science:
- Biochemistry
- Critical Care Medicine
- Molecular Biology
Background:
- Sepsis-induced myocardial dysfunction (SIMD) is a critical complication of sepsis.
- The mammalian target of rapamycin (mTOR) pathway is implicated in SIMD in animal models, but human clinical data are lacking.
Purpose of the Study:
- To investigate the association between the mTOR signaling pathway and SIMD in human patients.
- To identify potential biomarkers for predicting SIMD and mortality in sepsis patients.
Main Methods:
- Eighty-eight sepsis patients were enrolled in the ICU.
- Serum levels of mTOR pathway components (mTOR, PS6K, LC3B), BIM, and inflammatory cytokines were measured.
- Hemodynamic and echocardiographic parameters were recorded.
Main Results:
- Patients with SIMD exhibited higher ICU and 28-day mortality.
- Elevated serum phosphorylated ribosome S6 protein kinase (PS6K) and Bcl-2-interacting mediator of cell death (BIM) levels, and lower microtubule-associated protein light chain 3 type II (LC3B) levels were observed in SIMD patients.
- PS6K concentration at admission independently predicted 28-day mortality and SIMD incidence.
Conclusions:
- The mTOR pathway, particularly PS6K activation, is significantly associated with SIMD and mortality in sepsis patients.
- Serum PS6K levels may serve as a predictive biomarker for SIMD and patient outcomes.
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