Tissue factor and tissue factor pathway inhibitor

Price, G. C.; Thompson, Stuart A.; Kam, P. C. A.

doi:10.1111/j.1365-2044.2004.03679.x

Cited by 66 publications

(77 citation statements)

References 96 publications

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“…Exclusive binding of Hep, but not HSPG, by HARE could be advantageous in that by-products of coagulation and infection are readily cleared from the circulation, keeping the systemic fluids relatively clear of these undesired products in contrast to their higher concentrations in wound or infected areas. For instance, tissue factor pathway inhibitor counteracts tissue factor and inhibits factors VIIa and X (69). Under normal conditions, factor Xa, a proteolytic product of factor X, in the presence of factors VII and VIIIa, will bind tissue factor pathway inhibitor on endothelial cells and be internalized via an unknown receptor (70).…”

Section: Discussionmentioning

confidence: 99%

The Human Hyaluronan Receptor for Endocytosis (HARE/Stabilin-2) Is a Systemic Clearance Receptor for Heparin

Harris

Weigel

2008

Journal of Biological Chemistry

106

112

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Heparin (Hep)2 is the most anionic proteoglycan, due to the extensive sulfation of its glycosaminoglycan (GAG) chains, and contains many different sulfated disaccharide isomers of N-acetylgalactosamine and glucuronic acid or iduronic acid. Hep binds to many different soluble, matrix, and cell surface proteins and receptors, and has many functions, including its roles as an anti-coagulant and as a co-receptor for some growth factors (1, 2). Hep is a highly prescribed drug in surgical patients and those at risk for thromobosis. The genes and metabolic pathway for Hep biosynthesis in mast cells are understood reasonably well, and many of the biological and clinical activities of Hep have been well studied for several decades (3-6). In contrast, we know less about the catabolism of Hep and how total body homeostasis of this multifunctional proteoglycan is maintained. In particular, the mechanisms controlling systemic turnover of Hep, whether as endogenous proteoglycan or free chain drugs, are not known.Although receptors for Hep have been characterized on a variety of cell types (e.g. macrophages, vascular smooth muscle cells), none of these mediate substantial clearance of Hep (7-9). A few reports implicated a role for Kupffer cells in Hep clearance, but were not followed up (10, 11). The possible contribution of liver sinusoidal endothelial cells to Hep uptake in these primary cell preparations was not examined. Because Hep is a widely prescribed drug, it is even more important to understand the factors that control its clearance and, therefore, pharmokinetics. Animal studies of Hep clearance, except by renal function, have been difficult to perform, because Hep binds to so many soluble, cell surface or matrix proteins and become widely distributed after injection.Unfractioned Hep (3000 -30000 Da), low molecular mass Hep (300 -8000 Da), and the pentasaccharide, Fondaparinux, are the three classes of Hep drugs used to treat venous thrombosis, acute myocardial infarction, trauma, obesity, and coronary and peripheral vascular procedures; all situations wherein patients need immediate platelet anti-coagulation therapy (12). Following an intravenous bolus, unfractioned Hep has a halflife of ϳ1 h and is cleared from the circulation by the liver and kidney (13). Low molecular mass Hep and the pentasaccharide, subcutaneously injected, have half-lives of ϳ3-6 and ϳ17 h, respectively (14). Larger more structurally diverse Hep is more readily cleared than the lower molecular weight fragments. Although clinical handbooks declare that Hep is metabolized and cleared by the reticuloendothelial system, the mechanisms for Hep clearance are not known.The primary scavenger receptor for systemic turnover of HA and most types of chondroitin sulfate, but not HS, is HARE/ Stab-2, which mediates most of the total body HA turnover per day (15)(16)(17). HARE is found primarily in the sinusoidal endothelial cells of the lymph nodes, liver, and spleen (18 -21), and * This work was supported, in whole or in part, by National Institutes of Hea...

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Section: Discussionmentioning

confidence: 99%

The Human Hyaluronan Receptor for Endocytosis (HARE/Stabilin-2) Is a Systemic Clearance Receptor for Heparin

Harris

Weigel

2008

Journal of Biological Chemistry

106

112

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“…Although the role of TF in coagulation-unrelated events such as infl ammation, sepsis, and angiogenesis is extensively investigated, the role of TF in tumor invasion and metastasis has undoubtedly attracted most attention because of its obvious clinical relevance (Versteeg et al 2004). Various tissues and body fl uids (amniotic fl uid, bile, semen, sweat, or tears) have been known to have TF activity (Zacharski 1979;Price et al 2004;Yarat et al 2004;Alturfan et al 2006;Emekli-Alturfan 2007). However, most of them are not easily obtained, saliva, on the other hand, is especially suitable for study because of its ready availability.…”

Section: Salivamentioning

confidence: 99%

Altered Biochemical Parameters in the Saliva of Patients with Breast Cancer

Emekli-Alturfan

Demir

Kasikci

et al. 2008

Tohoku J. Exp. Med.

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Saliva plays an important role in the protection of oral cavity and alterations in either salivary fl ow rate or protein composition may have dramatic effects on oral health. Prevention and management of oral complications of cancer and cancer therapy will improve oral function and quality of life, and reduce morbidity and the cost of care. The aim of this study was to investigate the saliva of patients with breast cancer biochemically and cytologically and compare with healthy controls. Accordingly, lipid peroxidation (LPO), total protein, salivary fl ow rate, and pH levels were measured in the saliva samples obtained from 20 breast cancer patients and 11 healthy individuals. Tissue factor (TF) is a major regulator of normal hemostasis and thrombosis, and TF activity of saliva samples was evaluated. Under the conditions used, patients with breast cancer present a signifi cant reduction in total protein, pH and LPO levels. Salivary TF activity was higher in breast cancer patients than that in control subjects, but the degree of increase was not statistically signifi cant. In addition, the analysis of saliva samples by SDS polyacrylamide gel electrophoresis showed the retarded mobility of the 66-kDa proteins and the increased proteins of about 36 kDa in the patient group. Some patients with breast cancer had increased number of leucocytes. Importantly, dysplastic cells and yeast cells were detected only in saliva samples of cancer patients. Decreased salivary LPO may be considered as a risk factor for breast cancer. breast cancer; saliva; tissue factor; lipid peroxidation; protein.Tohoku J. Exp. Med., 2008, 214 (2), 89-96.

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“…Acting in the plasma and tissue, plasminogen activator inhibitor-1 has multiple functions in the cardiovascular and renal systems where it can either promote thrombosis or fibrosis (Price et al, 2004). Plasminogen activator inhibitor-1 is one of the most important inhibitors of fibrinolysis.…”

Section: Pai-1mentioning

confidence: 99%

The Role of Plasminogen Activator Inhibitor-1 in the Metabolic Syndrome and Its Regulation

Phelan¹,

Kerins²

2014

JFR

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Obesity is a major risk factor for cardiovascular disease (CVD). Lipid abnormalities, hypertension, impaired glucose tolerance or diabetes, are cardiovascular risk factors that are frequently present in patients with obesity. Haemostatic and fibrinolytic disturbances are also considered to be important risk factors for CVD hence, a potential link between CVD, obesity and the metabolic syndrome arises. Regulation of the fibrinolytic system can occur at the level of plasminogen activators and plasminogen activator inhibitor-1 (PAI-1). PAI-1, a glycoprotein, is one of the most important inhibitors of fibrinolysis. Regulation of this serine protease inhibitor may have a beneficial effect on other conditions associated with the metabolic syndrome. Human adipose tissue is a source of PAI-1. PAI-1 production may in turn be controlled by a number of hormones and cytokines which are secreted by adipose tissue in addition to dietary factors. In this review we summarise the current knowledge regarding the role of altered fibrinolytic function in obesity, CVD and hence the metabolic syndrome. Regulatory factors including different dietary components, weight loss and dietary intervention will also be discussed.

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Tissue factor and tissue factor pathway inhibitor

Cited by 66 publications

References 96 publications

The Human Hyaluronan Receptor for Endocytosis (HARE/Stabilin-2) Is a Systemic Clearance Receptor for Heparin

The Human Hyaluronan Receptor for Endocytosis (HARE/Stabilin-2) Is a Systemic Clearance Receptor for Heparin

Altered Biochemical Parameters in the Saliva of Patients with Breast Cancer

The Role of Plasminogen Activator Inhibitor-1 in the Metabolic Syndrome and Its Regulation

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