Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions.

Goto, Shinichi; Ikeda, Yasuo; Saldı́var, Enrique; Ruggeri, Zaverio M.

doi:10.1172/jci973

Cited by 279 publications

(218 citation statements)

References 39 publications

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“…31 Conditions of high and low shear may thus occur in close proximity to thrombotic deposits, and the sudden change from low to high shear around the growing thrombus may take place synergistically by reinforcing the binding to activated GPIIb/IIIa. 25 Although we observed a significant correlation between the plasma level of vWF or the amount of larger vWF multimers and the extent of high shear-induced SIPA, a direct relationship may not exist between these parameters. Rather, the elevation in plasma vWF and/or the extent of larger multimers may be a consequence of the onset of ACSs.…”

Section: Discussioncontrasting

confidence: 62%

“…2,23,24 Recent data indicate that plasma vWF and platelet GPIb are essential in the response to varying hemodynamic conditions and that vWF-dependent platelet aggregation mediated by the vWF-GPIb interaction is necessary to functionally complement the activated GPIIb/IIIa in the presence of elevated fluid dynamic forces. 25 In contrast, it has been shown that high shear-induced aggregation of washed platelets increases as a function of the concentration of exogenous purified vWF. 26 In addition, because wall shear rates of 3000 to 10 000 s Ϫ1 have been measured at the top of plaques, causing a 50% occlusion of the coronary arteries, 27 vWFGPIb binding may lead to arterial occlusion in a patient with atherosclerosis and precipitate a disease such as an ACS.…”

Section: Discussionmentioning

confidence: 98%

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AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Eto

Isshiki²,

Yamamoto³

et al. 1999

ATVB

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Abstract-The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesisthat occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm 2 ) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 g/mL AJvW-2. Under low-shear conditions (12 dyne/cm 2 ), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries. A ctivation of platelets induced by physical shear stress or by physiological agonists is important in arterial thrombogenesis. 1,2 Increased levels of plasma von Willebrand factor (vWF) in patients with thrombotic disorders have suggested that this protein may be involved in thrombosis. For example, in survivors of acute myocardial infarction (AMI), the level of plasma vWF may be an index of the increased risk for reinfarction and mortality. 3 In addition, an enhanced plasma vWF concentration is thought to be an independent predictor of such acute coronary syndromes (ACSs) as unstable angina (UAP). 4 Most importantly, high physiological and/or pathological shear stress can induce vWF-mediated platelet aggregation in vitro 1,2,5,6 and may stimulate the interaction between plasma vWF and glycoprotein (GP) Ib on platelets in vivo, eg, in animal models with coronary artery occlusion. 7 To further clarify the molecular mechanism for arterial thrombogenesis and to seek an effective strategy for its prevention or treatment, efforts have focused on developing simple methods for monitoring vWFplatelet interactions in the blood of patients with ACSs. 2 The recent development of a cone-and-plate viscometer to monitor platelet aggregation under various shear conditions in the absence of an...

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 98%

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Eto

Isshiki²,

Yamamoto³

et al. 1999

ATVB

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“…Injury to a blood vessel wall causes exposure to the blood of molecules embedded in the wall, including collagen and tissue factor. Blood platelets adhere to the collagen and become activated, thus beginning the process of platelet aggregation (Ruggeri 1994;Goto, Ikeda, Saldívar, and Ruggeri 1998). Tissue factor initiates the coagulation process which involves a tightly regulated network of enzyme reactions (Jesty and Nemerson 1995;Mann, Nesheim, Church, Haley, and Krishnaswamy 1990).…”

Section: Introductionmentioning

confidence: 99%

Fibrin gel formation in a shear flow

Guy

Fogelson²,

Keener³

2007

Mathematical Medicine and Biology: A Journal of the IMA

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Blood clots are made up of platelets and fibrin gel, and the relative amount of fibrin is strongly influenced by the shear rate. In order to explore this phenomenon, this paper presents a model of fibrin gel formation over the surface of an injured blood vessel in a shear flow. A condition for gelation including source and sink terms of polymer is derived. A simplified model of coagulation, involving activation and inhibition of the enzyme thrombin and thrombinmediated production of fibrin monomer, is combined with the model of gelation to explore how the shear rate and other parameters control the formation of fibrin gel. The results show that the thrombin inhibition rate, the gel permeability, and the shear rate are key parameters in regulating the height of the fibrin gel.

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“…The two principle adhesive ligands promoting platelet aggregation are von Willebrand factor (vWf) 1 and fibrinogen, with each having distinct, complementary roles in this process (1)(2)(3)(4)(5). Fibrinogen acts as a bridging molecule between adjacent activated platelets and is the principle adhesive ligand promoting platelet aggregation under low and intermediate shear flow conditions (1,2).…”

mentioning

confidence: 99%

Integrin αIIbβ3-dependent Calcium Signals Regulate Platelet-Fibrinogen Interactions under Flow

Goncalves

Hughan

Schoenwaelder

et al. 2003

Journal of Biological Chemistry

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Platelet adhesion to fibrinogen is important for platelet aggregation and thrombus growth. In this study we have examined the mechanisms regulating platelet adhesion on immobilized fibrinogen under static and shear conditions. We demonstrate that integrin ␣ IIb ␤ 3 engagement of immobilized fibrinogen is sufficient to induce an oscillatory calcium response, necessary for lamellipodial formation and platelet spreading. Released ADP increases the proportion of platelets exhibiting a cytosolic calcium response but is not essential for calcium signaling or lamellipodial extension. Pretreating platelets with the Src kinase inhibitor PP2, the inositol 1,4,5-trisphosphate (IP 3 ) receptor antagonist 2-aminoethoxydiphenyl borate (APB-2), or the phospholipase C (PLC) inhibitor U73122 abolished calcium signaling and platelet spreading, suggesting a major role for Src kinase-regulated PLC isoforms in these processes. Analysis of PLC␥2 ؊/؊ mouse platelets revealed a major role for this isoform in regulating cytosolic calcium flux and platelet spreading on fibrinogen. Under flow conditions, platelets derived from PLC␥2 ؊/؊ mice formed less stable adhesive interactions with fibrinogen, particularly in the presence of ADP antagonists. Our studies define an important role for PLC␥2 in integrin ␣ IIb ␤ 3 -dependent calcium flux, necessary for stable platelet adhesion and spreading on fibrinogen. Furthermore, they establish an important cooperative signaling role for PLC␥2 and ADP in regulating platelet adhesion efficiency on fibrinogen.Platelet adhesion and aggregation at sites of vascular injury are critical for the arrest of bleeding in traumatized vessels and also for the development of arterial thrombi, precipitating diseases such as acute myocardial infarction and stroke. The two principle adhesive ligands promoting platelet aggregation are von Willebrand factor (vWf) 1 and fibrinogen, with each having distinct, complementary roles in this process (1-5). Fibrinogen acts as a bridging molecule between adjacent activated platelets and is the principle adhesive ligand promoting platelet aggregation under low and intermediate shear flow conditions (1, 2). In addition, it also contributes to stable aggregate formation under high shear (1,5,6). It is well established that the binding of fluid-phase fibrinogen to the platelet surface is dependent on the activation of integrin ␣ IIb ␤ 3 (GPIIb-IIIa) through intracellular signaling processes linked to various G protein-coupled and tyrosine kinase-linked receptors (7).Platelets can also adhere to immobilized fibrinogen, a process that is important for primary platelet adhesion onto artificial surfaces, including vascular prostheses (8, 9), and for normal thrombus development (5, 6). In the case of thrombus formation, active integrin ␣ IIb ␤ 3 on the surface of firmly adherent platelets adsorbs soluble fibrinogen to the thrombus surface, thereby providing a reactive substrate for the recruitment of additional platelets. In contrast to soluble fibrinogen, the adhesion of platelets onto...

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Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions.

Cited by 279 publications

References 39 publications

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Fibrin gel formation in a shear flow

Integrin αIIbβ3-dependent Calcium Signals Regulate Platelet-Fibrinogen Interactions under Flow

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