New clues regarding the mysterious mechanism of activated thrombin-activatable fibrinolysis inhibitor self-destruction

Plug, T.; Meijers, Joost C. M.

doi:10.1111/jth.12900

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…The present study investigated the efficacy of aspirin treatment in vivo and demonstrated that aspirin treatment improved thrombolysis by increasing the expression levels of TAFI and PAI-1 in cerebrovascular endothelial cells. One previous study provided further insight into the mechanism of activated TAFI self-destruction, which indicated that TAFI deletion mutant appears to be more stable than the activated TAFI control (31). The tPA plasma concentration levels were increased in the mouse model of cerebral infarction following treatment with aspirin in the present study.…”

Section: Discussionsupporting

confidence: 64%

Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

et al. 2017

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Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis. The results demonstrated that aspirin inhibited inflammation and apoptosis of cerebrovascular endothelial cells in a mouse model of cerebral infarction. Aspirin treatment suppressed toll‑like receptor (TLR)4 and nuclear factor (NF)‑κB expression in cerebrovascular endothelial cells. Endoplasmic reticulum (ER) stress was suppressed by aspirin treatment through the downregulation of protein kinase R‑like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2 subunit 1 and C/EBP homologous protein expression levels in cerebrovascular endothelial cells. It was identified that knockdown of TLR4 inhibited aspirin‑mediated downregulation of NF‑κB signaling pathway and ER stress in cerebrovascular endothelial cells. Expression levels of adenosine diphosphate plasminogen activator inhibitors, von Willebrand factor and thromboxane were downregulated in cerebrovascular endothelial cells and in serum in experimental mice. The results demonstrated that aspirin was beneficial forthrombolysis by decreasing thrombin‑activatable fibrinolysis inhibitor and plasminogen activator inhibitor‑1 expression in a mouse model of cerebral infarction. These results suggested that aspirin may improve cerebral infarction by downregulating TLR4/NF‑κB‑mediated ER stress in a mouse model.

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Section: Discussionsupporting

confidence: 64%

Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

et al. 2017

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“…However, previous studies have demonstrated that the influence of genetic variations in the TAFI gene on the risk of CVD is inconclusive. Plug and Meijers have put forward new clues regarding the mysterious mechanism of activated TAFI self-destruction ( 16 ). In addition, previous research has also indicated the PAI-1 regulates the balance of the plasma fibrinolytic and blood coagulation system and further initiates or promotes the progression of CVD ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

Wang

et al. 2017

Int J Mol Med

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Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the accumulation of inflammatory factors in the lesions in venous thrombus. Matrix metalloproteinase (MMP) expression and activity were downregulated in rivaroxaban-treated rats with deep venous thrombus. Rivaroxaban inhibited the elasticity of the extracellular matrix and collagen-elastin fibers. On the whole, these results indicate that rivaroxaban attenuates deep venous thrombus through MMP-9-mediated NF-κB signaling pathway.

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[Retracted] Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

Wang

et al. 2018

Int J Mol Med

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New clues regarding the mysterious mechanism of activated thrombin-activatable fibrinolysis inhibitor self-destruction

Cited by 3 publications

References 21 publications

Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

[Retracted] Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

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