TFPIα alleviated vascular endothelial cell injury by inhibiting autophagy and the class III PI3K/Beclin-1 pathway

Zhao, Yanxin; Zhu, Minling; Chen, Wenjia; Chang, Qing; Shen, Li; Yan, Runan; Yang, LiuPing; Li, Jiashu; Xu, Rui; Fu, Yu; Liu, Yue

doi:10.1016/j.thromres.2020.07.017

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…These results suggest that full-length TFPI in plasma may be a marker of endothelial cell dysfunction. Basic experiments carried out by Zhao et al 30 found that TFPI can reduce endothelial cell injury by inhibiting endothelial autophagy and the class III PI3K/Beclin-1 pathway, while in clinical studies, Keyloun et al 13 used TFPI as a biomarker of endothelial injury and showed that the high level of TFPI in burn patients was related to a nine-fold increase in mortality (OR:9.59), and provided a predictive index of burn mortality. On the other hand, the inflammation caused by trauma has always been the focus of research attention, with studies showing that the levels of pro-inflammatory factors in plasma of post-traumatic patients were increased significantly.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

Cao

Zhang

et al. 2021

Clin Appl Thromb Hemost

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Objective Deep venous thrombosis (DVT) is a common complication in patients with traumatic injury. Tissue factor pathway inhibitor (TFPI) is a natural anticoagulant protein in the extrinsic coagulation pathway. However, the relationship between DVT after trauma and the anticoagulant activity of TFPI remains unclear. In this prospective study, we investigated the role of TFPI in trauma patients with DVT to evaluate whether the anticoagulant activity of TFPI measured by a new functional assay can be used to help predict the risk of DVT. Patients and methods: This prospective nested case-control study enrolled trauma patients and healthy volunteers. Forty-eight trauma patients diagnosed with DVT and forty-eight matched trauma patients without DVT were included in the study. 120 healthy volunteers were also included as controls. Blood samples and case information were collected at admission. Patients accepted angiography before surgery to diagnose DVT. The parameters examined included TFPI anticoagulant activity, free-TFPI antigen, blood cell counts, and routine clinical coagulation tests. Results: For the parameters of TFPI anticoagulant activity, three were markedly increased in the DVT group compared to the non-DVT group (TFPI initial anticoagulant time ratio, P = .022; TFPI whole anticoagulant time ratio, P = .048; and TFPI anticoagulant rate, P = .034). The free-TFPI antigen concentration also showed a significant increasing trend in trauma patients with DVT compared with trauma patients without DVT (P = .035). Multivariate logistic regression analysis identified four independent factors for the development of DVT (TFPI initial anticoagulant time ratio, free-TFPI antigen, prothrombin time, and red blood cell count). We calculated the TFPI correlation coefficient and found that the area under the receiver operating characteristic curve was .821. Conclusions: A novel functional assay was developed to measure the anticoagulant activity of TFPI. The anticoagulant activity of TFPI can be used as a potential biomarker for diagnosing DVT in trauma patients.

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Section: Discussionmentioning

confidence: 99%

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

Cao

Zhang

et al. 2021

Clin Appl Thromb Hemost

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“…Our results showed that Tp47 induced autophagy in HMC3 cells by inhibiting the PI3K/AKT pathway. Several studies have shown that the PI3K/AKT signalling pathway plays an important role in the regulation of autophagy 28,29 . Autophagosome formation is initiated by the PI3P molecule synthesized by PI3K class II kinase, which is usually activated after interaction with Beclin‐1.…”

Section: Discussionmentioning

confidence: 99%

Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway

Xie

Zheng

et al. 2023

J Cellular Molecular Medi

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The migratory ability of microglia facilitates their rapid transport to a site of injury to kill and remove pathogens. However, the effect of Treponema pallidum membrane proteins on microglia migration remains unclear. The effect of Tp47 on the migration ability and autophagy and related mechanisms were investigated using the human microglial clone 3 cell line. Tp47 inhibited microglia migration, the expression of autophagy‐associated protein P62 decreased, the expression of Beclin‐1 and LC3‐II/LC3‐I increased, and the autophagic flux increased in this process. Furthermore, autophagy was significantly inhibited, and microglial cell migration was significantly increased after neutralisation with an anti‐Tp47 antibody. In addition, Tp47 significantly inhibited the expression of p‐PI3K, p‐AKT, and p‐mTOR proteins, and the sequential activation of steps in the PI3K/AKT/mTOR pathways effectively prevented Tp47‐induced autophagy. Moreover, Tp47 significantly inhibited the expression of p‐FOXO1 protein and promoted FOXO1 nuclear translocation. Inhibition of FOXO1 effectively suppressed Tp47‐induced activation of autophagy and inhibition of migration. Treponema pallidum membrane protein Tp47‐induced autophagy and inhibited cell migration in HMC3 Cells via the PI3K/AKT/FOXO1 pathway. These data will contribute to understanding the mechanism by which T. pallidum escapes immune killing and clearance after invasion into the central nervous system.

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“…Under I/R condition, excessive autophagy is induced by the class III PI3K complex, which contains class Ш PI3K Vps34 and Beclin1. The coiled-coil domain of Beclin1 can bind to class III PI3K Vps34 by interacting with an evolutionarily conserved domain ( Zhao et al, 2020 ). Recently, mounting studies have found autophagy is inhibited when Bcl-2 binds to Beclin1.…”

Section: Discussionmentioning

confidence: 99%

QishenYiqi dripping pill protects against myocardial ischemia/reperfusion injury via suppressing excessive autophagy and NLRP3 inflammasome based on network pharmacology and experimental pharmacology

Wang

et al. 2022

Front. Pharmacol.

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Background: Myocardial ischemia/reperfusion (I/R) injury is associated with multiple serious clinical manifestations. Autophagy is upregulated in a short period of ischemia and further enhanced during reperfusion phase, which was considered as a “double-edged sword” in the pathological process of myocardial I/R injury. In addition, NLRP3 inflammasome triggers myocardial inflammatory response, which leads to cardiomyocyte death via pyroptosis and promotes subsequent myocardial remodelling. Qishen Yiqi Dripping Pill (QSYQ) has been recognized as a potential protective agent of cardiovascular diseases.Objective: We predicted the bioactive compounds, targets and pathways of OSYQ intervening on myocardial I/R injury by network pharmacology. Furthermore, we investigated the effect of QSYQ on myocardial I/R injury and explored its underlying mechanism via autophagy and NLRP3 Inflammasome.Methods: Bioactive compounds, targets of QSYQ and relevant targets of myocardial I/R injury were collected from public databases. The protein-protein interaction network, Gene ontology and KEGG pathway enrichment analysis were carried out to screen the key compounds, target genes, functional annotation and pivotal pathways. Molecular docking was used to validate the binding association between target genes and key bioactive ingredients. Furthermore, sixty SD rats were randomized into four groups: 1) sham, 2) model, 3) captopril and 4) QSYQ pretreatment (14 days before and after surgery). Each arm was subjected to ischemia/reperfusion surgery except sham arm (30 min coronary ligation, then reperfusion). Left ventricular (LV) function were evaluated and the hearts were used to evaluate size of myocardial infarction, cardiomyocyte fibrosis, and myocardial autophagosomes.Results: The network pharmacology revealed the mechanism of QSYQ intervening on myocardial I/R injury might be related to NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, autophagy-animal, etc., Molecular-docking suggested the core target proteins had good binding association with bioactive compounds of QSYQ. The experiment confirmed that QSYQ attenuated myocardial infarct size, decreased inflammatory infiltration and collagen fiber deposition and alleviated the autophagosome and myocardium ultrastructure injury, leading to LV systolic function improvement. The possible mechanism of cardioprotection was due to regulating autophagy-related proteins, activating PI3K/Akt-mTOR signaling pathway, and inhibiting activation and assembly of NLRP3 inflammasome.Conclusion: QSYQ ameliorated myocardial I/R injury via suppressing excessive autophagy and NLRP3 Inflammasome.

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TFPIα alleviated vascular endothelial cell injury by inhibiting autophagy and the class III PI3K/Beclin-1 pathway

Cited by 5 publications

References 31 publications

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway

QishenYiqi dripping pill protects against myocardial ischemia/reperfusion injury via suppressing excessive autophagy and NLRP3 inflammasome based on network pharmacology and experimental pharmacology

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