Cloning of Guinea Pig Tissue Factor cDNA: Comparison of Primary Structure among Six Mammalian Species

2000 ◽  
Vol 83 (03) ◽  
pp. 455-461 ◽  
Author(s):  
Rui-Jin Shi ◽  
Wen-Zhou Li ◽  
Victor Marder ◽  
Lee Sporn
Keyword(s):  
Guinea Pig ◽  
Tissue Factor ◽  
Catalytic Domain ◽  
Mammalian Species ◽  
Coagulation Factor ◽  
Apparent Molecular Weight ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Reading Frame ◽  
Coagulation Factor Vii

SummaryTissue factor (TF) is a transmembrane glycoprotein that serves as an essential cofactor for plasma coagulation factor VII. TF procoagulant activity exhibits varying species specificity. In particular, guinea pig (GP) TF is unable to activate clotting in heterologous plasma systems, but the molecular basis for this phenomenon is not yet understood. The full-length GP TF cDNA was cloned and sequenced. The open reading frame encoded a predicted precursor protein of 289 amino acids (aa) which was expressed in a reticulocyte lysate system as a protein of apparent molecular weight of 34 kD. The identity of the predicted aa sequence of mature GP TF with rabbit, human, bovine, rat and mouse TF was 66.4, 64.4, 60.6, 53.2 and 52.2%, respectively. With a focus on sites of potential functional significance, we compared sequences within the known binding regions. The eleven residues at the interface region between the TF1 and TF2 modules, which bind to the EGF domain of VIIa, were perfectly conserved among the six species, with the exception of an isoleucine replacing a lysine in the guinea pig sequence. However, only four of the eleven binding residues in the TF1 module, known to interact with the catalytic domain of factor VII, and three of the five residues in the TF2 module, involved in binding the factor VII Gla domain, were conserved among species. We hypothesize that divergence at these regions contributes to the specificity and non-reciprocity of TF procoagulant activity between species.

scholarly journals Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

2007 ◽  
Vol 92 (11) ◽  
pp. 4352-4358 ◽  
Author(s):  
Guenther Boden ◽  
Vijender R. Vaidyula ◽  
Carol Homko ◽  
Peter Cheung ◽  
A. Koneti Rao
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Glucose Levels ◽  
Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

scholarly journals Structural requirements for the interaction between tissue factor and factor VII: characterization of chymotrypsin-derived tissue factor polypeptides

1993 ◽  
Vol 292 (1) ◽  
pp. 7-12 ◽  
Author(s):  
D P O'Brien ◽  
J S Anderson ◽  
D M A Martin ◽  
P G H Byfield ◽  
E G D Tuddenham
Keyword(s):  
Tissue Factor ◽  
High Performance ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Chromogenic Assay ◽  
Membrane Bound ◽  
Ligand Blot

Tissue Factor (TF) is the cellular receptor for coagulation Factor VII/VIIa (FVII/VIIa). TF binds to FVIIa and promotes the rapid activation of the zymogen substrates Factors IX and X (FIX and FX) to the respective serine proteinases. In order to probe structure-function relationships in TF, we have subjected the truncated membrane-bound variant, TF 1-243, to proteolytic digestion in SDS-containing gels. Three major polypeptide fragments were generated by proteolysis of TF 1-243 with chymotrypsin, producing cleavages C-terminal to residues 34, 76 and 103. All three polypeptides, TF 35-243, 77-243 and 104-243, bound biotinylated human FVII in a highly specific ligand blot assay. High-performance electrophoretic chromatography was used to isolated chymotrypsin-derived fragments of TF. These purified fragments bound FVII in ligand blots, and two of the three polypeptides exhibited much reduced, but significant, procoagulant activity in a chromogenic assay for the generation of Factor Xa in the presence of FVIIa and Ca2+. The smallest chymotrypsin-derived TF polypeptide, TF 104-243, showed reduced binding of FVII in ligand blot analyses, inhibited the activity of the full-length molecule, but had no procoagulant activity. These data suggest that a part of the binding site for FVII is contained within the TF sequence 104-243. The sequence TF 1-34 either contains a part of the FVII-binding domain or its removal leads to dysfunctional folding, disrupting binding sites elsewhere in the molecule.

scholarly journals A frequent human coagulation Factor VII mutation (A294V, c152) in loop 140s affects the interaction with activators, tissue factor and substrates

2002 ◽  
Vol 363 (2) ◽  
pp. 411 ◽  
Author(s):  
Raffaella TOSO ◽  
Mirko PINOTTI ◽  
Katherine A. HIGH ◽  
Eleanor S. POLLAK ◽  
Francesco BERNARDI
Keyword(s):  
Tissue Factor ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Human Coagulation Factor Vii

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2794-2800 ◽  
Author(s):  
Diana Bonderman ◽  
Alexander Teml ◽  
Johannes Jakowitsch ◽  
Christopher Adlbrecht ◽  
Mariann Gyöngyösi ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Atherosclerotic Plaque ◽  
Coronary Vessels ◽  
Coagulation Factor ◽  
Particulate Material ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
No Reflow ◽  
Coronary Atherosclerotic Plaque ◽  
Distal Protection

Abstract Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 ± 13.00 pg/cm2 luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 ± 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 ± 142.8 pg/mL) as compared with levels after flow restoration (73.27 ± 31.90 pg/mL; P = .02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow.

scholarly journals A candidate activation pathway for coagulation factor VII

2019 ◽  
Vol 476 (19) ◽  
pp. 2909-2926
Author(s):  
Tina M. Misenheimer ◽  
Kraig T. Kumfer ◽  
Barbara E. Bates ◽  
Emily R. Nettesheim ◽  
Bradford S. Schwartz
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Factor Viia ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X ◽  
Contact Activation ◽  
Coagulation Factor Vii ◽  
Factor Viiia

Abstract The mechanism of generation of factor VIIa, considered the initiating protease in the tissue factor-initiated extrinsic limb of blood coagulation, is obscure. Decreased levels of plasma VIIa in individuals with congenital factor IX deficiency suggest that generation of VIIa is dependent on an activation product of factor IX. Factor VIIa activates IX to IXa by a two-step removal of the activation peptide with cleavages occurring after R191 and R226. Factor IXaα, however, is IX cleaved only after R226, and not after R191. We tested the hypothesis that IXaα activates VII with mutant IX that could be cleaved only at R226 and thus generate only IXaα upon activation. Factor IXaα demonstrated 1.6% the coagulant activity of IXa in a contact activation-based assay of the intrinsic activation limb and was less efficient than IXa at activating factor X in the presence of factor VIIIa. However, IXaα and IXa had indistinguishable amidolytic activity, and, strikingly, both catalyzed the cleavage required to convert VII to VIIa with indistinguishable kinetic parameters that were augmented by phospholipids, but not by factor VIIIa or tissue factor. We propose that IXa and IXaα participate in a pathway of reciprocal activation of VII and IX that does not require a protein cofactor. Since both VIIa and activated IX are equally plausible as the initiating protease for the extrinsic limb of blood coagulation, it might be appropriate to illustrate this key step of hemostasis as currently being unknown.

scholarly journals Funksionele beskrywing van ’n faktor VIIa inhiberende peptied, IP-7, geselekteer deur faagblootleggingstegnologie

2006 ◽  
Vol 25 (4) ◽  
pp. 209-220
Author(s):  
S.M. Meiring ◽  
C.E. Roets ◽  
P.N. Badenhorst
Keyword(s):  
Phage Display ◽  
Tissue Factor ◽  
Factor Viia ◽  
Coagulation Factor ◽  
Competitive Inhibitor ◽  
Factor Vii ◽  
Antithrombotic Agent ◽  
Phage Display Technology ◽  
Current Form ◽  
Coagulation Factor Vii

Die tegniek van faagblootlegging is gebruik om ’n sikliese heptapeptied te selekteer wat met weefselfaktor(WF) kompeteer vir binding aan stollingsfaktor VIIa. Die aminosuurvolgorde van die peptied is Cys-Ala- Trp-Pro-His-Thr-Pro-Asp-Cys (C-AWPHTPD-C) en dit verleng die protrombientyd (PT) op ’n konsentrasie-afhanklike wyse. Die peptied beperk plaatjieklewing aan beide menslike endoteelsel- en weefselfaktormatrikse in ’n vloeikamermodel onder arteriële vloeitoestande. Die peptied funksioneer as ’n volledig mededingende inhibeerder van faktor VIIa met ’n inhibisiekonstante (Ki) van 123,2 μM. In sy huidige vorm is die peptied waarskynlik nie sterk genoeg om verder as antitrombotiese middel ontwikkel te word nie, maar verskillende strategieë kan gevolg word om die werking daarvan te versterk. AbstractFunctional characterisation of a factor VIIa inhibiting peptide, IP-7 selected by phage display technology By using the technique of phage display, we selected a cyclic heptapeptide sequence Cys-Ala-Trp-Pro-His-Thr-Pro-Asp-Cys (C-AWPHTPD-C) that competes with tissue factor for binding to coagulation factor VII. This peptide prolongs the prothrombin time (PT) in a concentration dependent way. It also reduces platelet adhesion to both human endothelial cell and tissue factor matrixes in a flow chamber under arterial flow conditions. Furthermore, it acts as a full competitive inhibitor of factor VIIa with an inhibition constant (Ki) of 123,2 μM. In its current form the peptide is probably not sufficiently potent for development as an antithrombotic agent, but different strategies could be followed to reinforce its performance.

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