von Willebrand protein facilitates platelet incorporation in polymerizing fibrin.

Loscalzo, Joseph; Inbal, Aida; Handin, Robert I.

doi:10.1172/jci112668

Cited by 86 publications

(54 citation statements)

References 53 publications

(25 reference statements)

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“…6,7,8 We and others have also demonstrated the contribution of vWF to the interaction between platelets and fibrin 29,30 and also fibrin-rich thrombus formation. 10 The occlusive thrombi in this study were composed of a large amount of fibrin and platelets and were rich in vWF.…”

Section: Discussionmentioning

confidence: 90%

Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery

Yamashita¹

2006

Nihon Kessen Shiketsu Gakkaishi

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Objective-Plaque disruption does not always result in complete thrombotic occlusion. The mechanism of arterial thrombus propagation remains unclear. Methods and Results-We studied how vascular wall thrombogenicity and blood flow reduction affect thrombus propagation using a rabbit model of single and repeated balloon injury. After balloon injury of the normal femoral artery, the blood flow was reduced to 50%, 25%, or 10% (nϭ5). Small mural thrombi composed of aggregated platelets were produced, but no occlusive thrombi developed in any flow reduction. Three weeks after the first balloon injury, neointima with tissue factor expression and increased procoagulant activity was developed. Balloon injury of the neointima with the same blood flow reduction (nϭ5) induced fibrin-rich thrombus formation. Additionally, injury with flow reduced to 25% and 10% promoted thrombus propagation resulting in vessel occlusion within 160Ϯ18 and 71Ϯ17 seconds, respectively. An injection of anti-von Willebrand factor (vWF) monoclonal antibody (AJW200; 1.0 mg/kg) prevented occlusive thrombus formation. Conclusions-Increased vascular wall thrombogenicity together with a substantial blood flow reduction is crucial for occlusive thrombus formation, and vWF plays an important role in thrombus propagation. Reduced blood flow at plaque disruption sites might contribute to thrombus propagation leading to acute coronary syndromes. Key Words: thrombus propagation Ⅲ blood flow Ⅲ von Willebrand factor Ⅲ tissue factor T he rapid closure of coronary arteries caused by occlusive thrombi is the major cause of acute myocardial infarction. Disruption of coronary atherosclerotic plaques is recognized as one trigger of coronary thrombosis. 1,2 However, this process does not always result in complete thrombotic occlusion with subsequent acute myocardial infarction. Because microscopic coronary thrombi are frequently detected during autopsies of noncardiac death, 3,4 plaque disruption is considered a common complication and a high proportion of such events would be clinically silent. 5 Therefore, whether thrombus on plaque disruption is occlusive or nonocclusive is critical to the onset of clinical events. Although the mechanisms of plaque rupture and thrombus formation in lesions have been intensively investigated, how arterial thrombi are propagated remains unclear. See page 2207The thrombotic response to plaque disruption is probably regulated by the thrombogenicity of exposed plaque constituents, local hemorheology, systemic thrombogenicity, and fibrinolytic activity. 5 Many thrombotic factors are involved in acute thrombus formation. In particular, von Willebrand factor (vWF) binding to glycoprotein (platelet glycoprotein [GP]) Ib␣ and GP IIb-IIIa that plays an important role in platelet aggregation under conditions of rapid flow, might arise in atherosclerotic stenotic arteries. 6 -8 Tissue factor (TF) is a trigger of the extrinsic coagulation cascade. When simultaneously released from atheromatous plaques, TF potently activates the coagulation casc...

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Section: Discussionmentioning

confidence: 90%

Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery

Yamashita¹

2006

Nihon Kessen Shiketsu Gakkaishi

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“…Section 1734 solely to indicate this fact. Fibrinogen Binding: Competitive Binding Assay-Fibrinogen was iodinated using Iodobeads (Pierce) as described previously (10).…”

Section: Methodsmentioning

confidence: 99%

Chrysoptin Is a Potent Glycoprotein IIb/IIIa Fibrinogen Receptor Antagonist Present in Salivary Gland Extracts of the Deerfly

Reddy

Kounga

Mariano

et al. 2000

Journal of Biological Chemistry

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Salivary gland lysates of the deerfly (genus Chrysops) contain chrysoptin, an inhibitor of ADP-induced platelet aggregation, which presumably assists the fly in obtaining a blood meal. Chrysoptin has now been isolated, and its cDNA has been cloned and expressed. Chrysoptin was purified to homogeneity using anion exchange and hydrophobic interaction chromatography and found to be a protein with a molecular mass of 65 kDa as determined by gel electrophoresis. N-terminal amino acid sequencing allowed for the synthesis of degenerate oligonucleotides that led to cloning, from salivary gland specific mRNA, of the cDNA encoding this platelet inhibitor. No RGD sites are present in the predicted sequence. A search of GenBank TM did not reveal significant sequence homology between chrysoptin and other proteins. The molecular mass predicted from the cDNA was 59 kDa. Predicted glycosylation and phosphorylation sites may account for this difference in molecular mass, as recombinant chrysoptin expressed in Sf21 cells had a molecular mass of 65 kDa, matching that of the natural protein. Chrysoptin functions by inhibiting the binding of fibrinogen to the fibrinogen/glycoprotein IIb/ IIIa receptor on platelets with an IC 50 of 95 pmol. These results reveal that insect salivary glands are a source of fibrinogen receptor antagonists.To facilitate blood feeding, hematophagous arthropods produce a number of bioactive substances that overcome the hemostatic mechanisms of the host. Arthropods trigger primary hemostasis by damaging blood vessels while probing the skin. As platelet aggregation is fundamental to hemostasis, some hematophagous arthropods appear to have evolved the ability to secrete platelet inhibitors in their saliva. Previous reports of antiplatelet activity in arthropod saliva include findings of prostacyclin activity in ticks (1, 2); apyrase activity in ticks (3), mosquitoes (4), blood-sucking bugs (5), and tse-tse flies (6); and a nitrosylheme protein from Rhodnius prolixus that has the capacity to release nitric oxide (7). Other than the protein from Rhodnius, these antiplatelet activities have not been well characterized, and it is not clear whether these or other activities account for the platelet inhibitory activity found in salivary gland lysates.Deerflies (genus Chrysops), also referred to as "greenheads" because of their brilliant green eyes, frequent the coast of the northeastern United States for several weeks in midsummer. Because these flies inflict painful bites that sometimes bleed, we reasoned that deerfly salivary gland extract (DFE) 1 might contain an inhibitor of platelet aggregation. We reported previously that DFE inhibits ADP-, thrombin-, and collagen-induced aggregation of human platelets (8). DFE differs from the antiplatelet activities found in other arthropods in two respects. First, it does not alter cAMP levels in platelets, suggesting that it does not contain prostaglandin-like activity. Second, it does not contain apyrase activity. We report the isolation and characterization of chrysopti...

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“…Soluble fibrin monomer was prepared by thrombin-mediated cleavage of fibrinogen (5 mol/L) in the presence of 2 mmol/L glycine-proline-arginine-proline as previously described. 21 The reaction was stopped by bringing the concentration of D-phenylalanyl-L-prolyl-L-arginyl-chloromethylketone to 1 mmol/L. Fibrinopeptides and low molecular weight reagents were removed by using Centriplus 10 concentrators (Amicon).…”

Section: Preparation and Assay Of Fibrinogen Fragmentsmentioning

confidence: 99%

Regulation by Fibrinogen and Its Products of Intercellular Adhesion Molecule-1 Expression in Human Saphenous Vein Endothelial Cells

Harley

Sturge

Powell

2000

ATVB

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Abstract-It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (

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von Willebrand protein facilitates platelet incorporation in polymerizing fibrin.

Cited by 86 publications

References 53 publications

Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery

Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery

Chrysoptin Is a Potent Glycoprotein IIb/IIIa Fibrinogen Receptor Antagonist Present in Salivary Gland Extracts of the Deerfly

Regulation by Fibrinogen and Its Products of Intercellular Adhesion Molecule-1 Expression in Human Saphenous Vein Endothelial Cells

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