Tissue Factor Pathway Inhibitor: Potential Therapeutic Applications

Bajaj, Monika; Bajaj, S. Paul

doi:10.1055/s-0038-1657572

Cited by 108 publications

(75 citation statements)

References 36 publications

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“…Indeed therapeutic use of tissue factor pathway inhibitor has been found to be beneficial in animal models of several diseases with underlying pathological tissue factor-initiated clotting, such as sepsis, coronary thrombosis, microvascular anastomosis, ischaemia reperfusion injury, etc. [14]. The potential impact of such interventions in pleural inflammation and malignant mesothelioma remains unknown at this time.…”

Section: Discussionmentioning

confidence: 99%

“…Immunodepletion of TFPI sensitizes rabbits to endotoxin [12] and TF-induced [13] disseminated intravascular coagulation, suggesting an important role for TFPI in the pathophysiology of coagulation. Abnormal TF-induced coagulation is an essential feature of many pathological conditions including pleural fibrin deposition [1], sepsis, malignancy, acute respiratory distress syndrome, atherosclerotic plaques and glomerulonephritis [14]. Endothelium (intravascular), monocytes/macrophages (intra-and extravascular) and fibroblasts (extravascular) are the primary cells implicated in causing abnormal coagulation in these conditions [14,15].…”

mentioning

confidence: 99%

“…Abnormal TF-induced coagulation is an essential feature of many pathological conditions including pleural fibrin deposition [1], sepsis, malignancy, acute respiratory distress syndrome, atherosclerotic plaques and glomerulonephritis [14]. Endothelium (intravascular), monocytes/macrophages (intra-and extravascular) and fibroblasts (extravascular) are the primary cells implicated in causing abnormal coagulation in these conditions [14,15]. These cell types appear to regulate both intravascular and extravascular clotting by expressing TFPI under pathological conditions.…”

mentioning

confidence: 99%

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Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells

et al. 2000

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Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells. M.S. Bajaj, U. Pendurthi, K. Koenig, S. Pueblitz, S. Idell. #ERS Journals Ltd 2000. ABSTRACT: The mesothelial lining of the pleura and malignant mesothelioma promote fibrin deposition in pleural injury or neoplasia via expression of tissue factor (TF). It was hypothesized that these cells might also regulate intrapleural coagulation by elaborating TF pathway inhibitor (TFPI).TFPI activity and antigen in pleural fluids were assayed from patients with congestive heart failure (CHF), pneumonia, empyema, metastatic pleural cancer and malignant mesothelioma. The authors also assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as TFPI activity and antigen by human pleural mesothelial cells, malignant mesothelioma cells (MS-1 cell line) and human lung fibroblasts. Immunohistochemical analyses of normal, fibrotic, and neoplastic pleura were performed to determine whether TFPI antigen was expressed in vivo.The study revealed that TFPI was present in transudates from patients with CHF and exudative pleural effusions from patients with pneumonia, empyema or pleural carcinoma. TFPI mRNA, activity and antigen were expressed by pleural mesothelial cells, MS-1 cells and lung fibroblasts. Cytokines and serum stimulated a significant early increase in TF mRNA levels with minimal enhancement of TFPI mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and neoplastic pleural tissues.The current observations indicate that tissue factor pathway inhibitor is locally expressed in pleural disease, but that it does not prevent the development of a prothrombotic environment favouring local fibrin deposition in pleural inflammation or cancer. Eur Respir J 2000; 15: 1069±1078.

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Section: Discussionmentioning

confidence: 99%

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Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells

et al. 2000

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“…TF produced by monocytes/macrophages is a potent inducer of intravascular thrombosis on atherosclerotic plaque rupture, 12 and, notably, SDF-1␣ reduced both unstimulated and LPS-stimulated TF levels in PBMC from the patients with unstable angina (Figure 3). …”

Section: Effect Of Sdf-1␣ On Mmp-9 Timp-1 and Tf Expression In Pbmcmentioning

confidence: 99%

Stromal Cell–Derived Factor-1α in Unstable Angina

Damås¹,

Wæhre²,

Yndestad³

et al. 2002

Circulation

131

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Background-Chemokines play a pathogenic role in atherogenesis and plaque destabilization by activating and directing leukocytes into the atherosclerotic plaque. However, stromal cell-derived factor (SDF)-1 was recently found to have antiinflammatory effects, and we hypothesized that this chemokine could play a beneficial role in coronary artery disease. Methods and Results-Plasma levels of SDF-1␣ were significantly decreased in patients with stable (nϭ30) and unstable angina (nϭ30) compared with healthy control subjects (nϭ20), particularly in those with unstable disease. By flow cytometry and RNase protection assay, we found decreased surface expression but increased gene expression of the SDF-1␣ receptor CXCR-4 in peripheral blood mononuclear cells (PBMC) from patients with stable angina and patients with unstable angina. In vitro, SDF-1␣ (500 ng/mL) reduced both unstimulated and endotoxin/mitogen-stimulated mRNA and protein levels of monocyte chemoattractant protein-1, interleukin-8, matrix metalloproteinase-9, and tissue factor while increasing tissue inhibitor of metalloproteinases-1 in PBMC from patients with unstable angina. The SDF-1␣-mediated suppression of monocyte chemoattractant protein-1 and interleukin-8 appears to involve cAMP/ protein kinase A type I-dependent pathways. Finally, although SDF-1␣ suppressed the spontaneous release of these inflammatory mediators in unstable angina, enhancing effects were seen in unstimulated PBMC from healthy control subjects, possibly reflecting that PBMC in unstable angina are preactivated in vivo. Conclusions-In contrast to several other chemokines, our findings suggest that SDF-1␣, at least in high concentrations, may mediate antiinflammatory and matrix-stabilizing effects in unstable angina. These effects may promote plaque stabilization, and therapeutic intervention that enhances SDF-1␣ activity could potentially be beneficial in acute coronary syndromes. (Circulation. 2002;106:36-42.)

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“…Based on studies in animals demonstrating that TFPI attenuates the coagulopathy and improves survival in sepsis models, [17][18][19] a recombinant form of TFPI has been evaluated for this indication in humans. With promising phase II data, 20 TFPI was compared with placebo in a large phase III clinical trial in patients with severe sepsis.…”

Section: Tfpimentioning

confidence: 99%