Contribution of Tissue Factor Associated with Factor VII

Idell, Steven; Gonzalez, Kathleen; Bradford, Harlan N.; MacArthur, Cassandra K.; Fein, Alan M.; Maunder, Richard J.; Garcia, Joe G.N.; Griffith, David E.; Weiland, Jeffrey E.; Martin, Thomas R.; McLarty, Jerry; Fair, Daryl S.; Walsh, Peter N.; Colman, Robert W.

doi:10.1164/ajrccm/136.6.1466

Cited by 124 publications

(15 citation statements)

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“…In addition to increased levels of profibrotic cytokines and growth factors, activation of a coagulation cascade may play a role in the pathogenesis of IPF and acute respiratory distress syndrome (ARDS) [2]. Consistent with this findings, intra-alveolar accumulation of fibrin has been described for patients with IPF [3–5] and ARDS [6], in which rapid fibroproliferation and matrix synthesis can lead to the extensive fibrotic lesions [7]. Thrombin, a serine protease activated in the final stages of the coagulation cascade, is also readily detected within the lung and intra-alveolar spaces of several fibrotic lung diseases, including systemic sclerosis [8], a bleomycin model of pulmonary fibrosis [9] and IPF [10].…”

mentioning

confidence: 86%

Thrombin induces epithelial-mesenchymal transition via PAR-1, PKC, and ERK1/2 pathways in A549 cells

Song

Kang

Park

et al. 2013

Experimental Lung Research

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Thrombin activates protease-activated receptor (PAR)-1 and induces a myofibroblast phenotype in normal lung fibroblasts. The origins of myofibroblasts are resident fibroblasts, fibrocytes, and epithelial-mesenchymal transition (EMT). We investigated the effects of thrombin, an important mediator of interstitial lung fibrosis, on EMT in A549 human alveolar epithelial cells. We show that thrombin induced EMT and collagen I secretion through the activation of PAR-1, and PKC and ERK1/2 phosphorylation in A549 cells. These effects were largely prevented by a specific PAR-1 antagonist, short interfering RNA (siRNA) directed against PAR-1, or specific PKCα/β, δ, and ε inhibitors. These data indicated that interaction with thrombin and alveolar epithelial cells might directly contribute to the pathogenesis of pulmonary fibrosis through EMT. Targeting PAR-1 on the pulmonary epithelium or specific inhibitors to PKCα/β, δ, and ε might stop the fibrotic processes in human idiopathic pulmonary fibrosis by preventing thrombin-induced EMT.

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mentioning

confidence: 86%

Thrombin induces epithelial-mesenchymal transition via PAR-1, PKC, and ERK1/2 pathways in A549 cells

Song

Kang

Park

et al. 2013

Experimental Lung Research

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“…Like in sepsis, activation of coagulation in pneumonia and ALI/ARDS seems to be mediated by the TF-FVIIa pathway [30][31][32]. Pulmonary TF-levels are elevated in pulmonary inflammation [33,34].…”

Section: Coagulopathy In Pulmonary Inflammationmentioning

confidence: 99%

Pulmonary Coagulopathy as a New Target in Lung Injury - A Review of Available Pre-Clinical Models

Hofstra

Juffermans²,

Schultz³

et al. 2008

CMC

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Despite recent advances in supportive care, acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are clinical entities with high morbidity and high mortality. In systemic inflammation, like sepsis, uncontrolled host defense can lead to systemic activation of coagulation on the one hand, and attenuation of fibrinolysis on the other. In ALI/ARDS similar but local disturbances in fibrin turnover occur, leading to excessive alveolar fibrin deposition compromising pulmonary integrity and function. Therapies in patients with sepsis have specifically focused on coagulation disturbances. Evidence from preclinical and clinical investigations suggests pharmacologically targeting pulmonary "coagulopathy" could be of benefit to patients with ALI/ARDS as well. Recent animal studies have demonstrated that administration of heparins, activated protein C (APC), Antithrombin (AT), Tissue factor-Factor VIIa (TF-FVIIa) pathway inhibitors, plasminogen activators (PA) and thrombomodulin (TM) can attenuate pulmonary coagulopathy and reduce lung injury and/or improve oxygenation. Some of these studies have also shown anti-inflammatory effects of treatment targeting at coagulation. To date there are no published studies that have specifically studied the effects of anticoagulants on ALI/ARDS however there are on-going clinical trials. A solid base has to be provided by preclinical studies to justify clinical studies on new pharmacologic therapies for ALI/ARDS. In this systematic literature review we give an overview of the models for ALI/ARDS that have been used so far on the topic of pulmonary coagulopathy and focus on the pharmacological interventions that have been evaluated with these models. Finally, the applicability of the different approaches for future research on this subject will be discussed.

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“…Inflammation promotes coagulation and vice versa [12]. There is compelling evidence that in lung disease, the mediators involved in this crosstalk originate predominantly in the pulmonary compartment as, simultaneously measured plasma levels of proinflammatory cytokines involved in the process are often low [65,67,83]. There is compelling evidence that in lung disease, the mediators involved in this crosstalk originate predominantly in the pulmonary compartment as, simultaneously measured plasma levels of proinflammatory cytokines involved in the process are often low [65,67,83].…”

Section: Pulmonary Vascular Milieumentioning

confidence: 99%

The Role of Coagulation in Pulmonary Pathology

Aa²

2007

IADT

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Understanding mechanisms that underlie lung disorders is crucial to achieving optimum care and improved outcomes in pulmonary medicine. Extensive investigations have revealed that inflammation displays an active role in the pathogenesis of these diseases. The byproduct of these inflammatory reactions has been shown to propagate pulmonary disease in consonance with alteration in haemostatic balance. It is now apparent that the two phenomena constitute an interwoven relationship with protective but damaging effects, when dysregulated. However, the precise role of coagulation abnormalities in pulmonary pathology is still evolving. A large body of evidence suggests that an imbalance in intra-alveolar procoagulant and fibrinolytic activities occurs in a variety of lung conditions. This imbalance may even herald a number of pulmonary diseases. Its sequelae have been observed in lung parenchyma of humans and in animal models of lung inflammation. As the pathogenesis of coagulation-related lung diseases continues to be unraveled, therapeutic measures to mitigate pulmonary disease-specific coagulopathy are emerging. Current efforts are directed at depicting multifaceted molecules capable of selective but simultaneous interference with relevant aspects of the dual coagulation-fibrinolytic pathway.

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Contribution of Tissue Factor Associated with Factor VII

Cited by 124 publications

References 15 publications

Thrombin induces epithelial-mesenchymal transition via PAR-1, PKC, and ERK1/2 pathways in A549 cells

Thrombin induces epithelial-mesenchymal transition via PAR-1, PKC, and ERK1/2 pathways in A549 cells

Pulmonary Coagulopathy as a New Target in Lung Injury - A Review of Available Pre-Clinical Models

The Role of Coagulation in Pulmonary Pathology

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