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

Cheng, Wei; Long, Yun; Wang, Hao; Han, Wen; Zhang, Jiahui; Cui, Na

doi:10.1016/j.cjca.2019.03.022

Cited by 19 publications

(12 citation statements)

References 22 publications

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“…Sepsis was defined according to consensus international guidelines (Sepsis-3.0) ( Singer et al, 2016 ). When left ventricular ejection fraction (LVEF) deteriorated to < 50%, patients were defined as having SIMD ( Cheng et al, 2019 ). The exclusion criteria were (1) heart surgery, heart attack, or acute exacerbation of previous heart disease in the last week; (2) previous abnormal echocardiography; and (3) pregnancy.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress

Chen

Teng

et al. 2021

Front. Physiol.

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Aims: We examined the change in endogenous hydrogen sulfide (H2S) production and its role in sepsis-induced myocardial dysfunction (SIMD).Results: Significant elevations in plasma cardiac troponin I (cTnI), creatine kinase (CK), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were noted in SIMD patients, whereas left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and plasma H2S were significantly decreased relative to those in the controls. Plasma H2S was linearly related to LVEF and LVFS. Subsequently, an SIMD model was developed in mice by injecting lipopolysaccharide (LPS), and NaHS, an H2S donor, was used to elucidate the pathophysiological role of H2S. The mice showed decreased ventricular function and increased levels of TNF-α, IL-1β, cTnI, and CK after LPS injections. Toll-like receptor (TLR) 4 protein and endoplasmic reticulum stress (ERS) proteins were over expressed in the SIMD mice. All of the parameters above showed more noticeable variations in cystathionine γ-lyase knockout mice relative to those in wild type mice. The administration of NaHS could improve ventricular function and attenuate inflammation and ERS in the heart.Conclusion: Overall, these findings indicated that endogenous H2S deficiency contributed to SIMD and exogenous H2S ameliorated sepsis-induced myocardial dysfunction by suppressing inflammation and ERS via inhibition of the TLR4 pathway.

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Section: Methodsmentioning

confidence: 99%

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress

Chen

Teng

et al. 2021

Front. Physiol.

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“…Furthermore, the role of mTOR is not limited to immunosuppression. mTOR has pleiotropic effects in other end organs during sepsis, ranging from myocardial dysfunction in clinical sepsis (48) to cognitive impairment in experimental sepsis (49). The effect of the NKT cell/mTOR axis on other sepsis phenotypes is undefined.…”

Section: Methodsmentioning

confidence: 99%

Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells

Kim¹,

Ner-Gaon²,

Varon³

et al. 2020

Journal of Clinical Investigation

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“…The definitive diagnostic criteria for septic cardiomyopathy was not available so far and is still a challenge in clinical practice [11]. Currently, ventricular dysfunction evaluated by echocardiography, biochemical markers such as cardiac troponin I and BNP, or hemodynamic markers of inadequate oxygen delivery were used to define septic cardiomyopathy [3,12]. Elderly patients have high prevalence of pre-existing heart disease with impaired ventricular function and elevated BNP levels.…”

Section: Discussionmentioning

confidence: 99%

Role of eotaxin-1/CCL11 in sepsis-induced myocardial injury in elderly patients

Liu¹,

Zhao²,

Qiu³

et al. 2020

Aging

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Myocardial injury is a serious complication of sepsis. The present study aimed to identify potential biomarkers of sepsis-induced myocardial injury. Differentially expressed genes (DEGs) in patients and mice with sepsis-induced myocardial injury were identified via bioinformatic analysis. The identified DEG was tested in elderly patients with sepsis-induced myocardial injury. We identified 19 co-expressed DEGs. The most significant DEG was eotaxin-1/CCL11. We enrolled 25 controls without infections and 28 patients with sepsis-induced myocardial injury. Six of patients died within 30 days. Circulating eotaxin-1/CCL11 levels were significantly higher in patients with sepsis-induced myocardial injury than controls and were higher in nonsurvivors than survivors (both P < 0.01). Eotaxin-1/CCL11 was positively correlated with troponin I (r=0.48, P=0.01), B-type natriuretic peptide (BNP, r=0.44, P=0.02), and white blood cell (WBC) count (r=0.41, P=0.03). For the prediction of 30-day mortality, eotaxin-1/CCL11 had the greatest discriminatory ability (AUC 0.97) compared with troponin I (AUC 0.89), BNP (AUC 0.80), and WBC count (AUC 0.86). Taken together, eotaxin-1/CCL11 was upregulated in sepsis-injured myocardium and circulating eotaxin-1/CCL11 was a biomarker for predicting severity and mortality of elderly patients with sepsis-induced myocardial injury. These results suggest that eotaxin-1/CCL11 may become a useful biomarkers and potential therapeutic target for sepsisinduced myocardial injury.

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

Abstract: See editorial by Walley, pages 809e812 of this issue.

Cited by 19 publications

References 22 publications

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress

Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress

Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells

Role of eotaxin-1/CCL11 in sepsis-induced myocardial injury in elderly patients

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