Mechanical factors affecting hemostasis and thrombosis

Turitto, Vincent T.; Hall, Connie L.

doi:10.1016/s0049-3848(98)00157-1

Cited by 143 publications

(105 citation statements)

References 20 publications

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“…32 Unique to vortex rotation, turbulent flow that mimics the flow condition in the branching of the vessels or downstream of partially occluded vessels is generated. 33,34 When vortexing at rotation rates between 640 to 3200 rpm (set "2-8"), VWF was readily cleaved within 3 minutes by full-length ADAMTS13 in a rotation ratedependent manner; the cleavage product (a dimer of 176 kDa) reached the plateau at rotation rate of about 2500 rpm (with estimated shear rate more than 12 000 s Ϫ1 ) 33,34 (Figure 2A); the cleavage of VWF was also ADAMTS13 concentration dependent at a fixed rotation rate of about 2500 ( Figure 2B); even 2.5 L of normal human plasma was sufficient to cleave VWF in presence of 30 to 60 g/mL heparin under this condition ( Figure 2B). Addition of more heparin (500 g/mL) and barium chloride (10 mM) increased VWF cleavage product by plasma ADAMTS13 (Sara Meyer and X.L.Z., unpublished data, May 2007).…”

Section: Cleavage Of Vwf By Adamts13 and Variants Under Flowmentioning

confidence: 99%

The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow

Zhang

Pan

Rux

et al. 2007

Blood

109

151

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ADAMTS13 cleaves von Willebrand factor (VWF) between Tyr 1 Deficiency of plasma ADAMTS13 activity, due to either inherited mutations of the ADAMTS13 gene 2-9 or acquired autoantibodies against the ADAMTS13 protein, 10,11 results in thrombotic thrombocytopenic purpura (TTP).ADAMTS13 is primarily synthesized in hepatic stellate cells, 12-14 endothelial cells, 15,16 and megakaryocytes or platelets. 17,18 The plasma ADAMTS13 in healthy individuals ranges from 0.5 to 1 mg/L. 19,20 ADAMTS13 consists of metalloprotease, disintegrin, first thrombospondin type 1 (TSP1) repeat, and Cys-rich and spacer domains. 2,21 The C-terminus of ADAMTS13 has additional TSP1 repeats and 2 CUB (Cis/Cis/Urinary epidermal growth factor, Bone morphogenetic protein) domains. 2,21 Previous studies have shown that the N-terminus of ADAMTS13 is required and sufficient for recognition and cleavage of denatured multimeric VWF [22][23][24] or peptide substrate . 22 More recent studies have demonstrated that the spacer domain of ADAMTS13 binds the exosite (E 1660 APDLVLQR 1668 ) near the C-terminus of the VWF-A2 domain. 25,26 However, the role of the middle and distal C-terminal domains of ADAMTS13 in substrate recognition remains controversial. On the one hand, ADAMTS13 mutant lacking the CUB domains or truncated after the spacer domain cleaved multimeric VWF with similar efficiency as the full-length ADAMTS13 under static and denatured conditions 23,24 ; the mutant truncated after the spacer domain, when mixed with ADAMTS13-depleted plasma, was found to be "hyperactive" in cleaving a "stringlike" structure, which represents platelets attached to the newly released VWF on the endothelial cell surface in a parallelflow chamber-based assay. 27 These data suggest that the distal portion of ADAMTS13 molecule may be dispensable under static and denatured conditions but may play a role in modulating ADAMTS13-VWF interaction under flow. On the other hand, synthetic peptides or recombinant fragments derived from the CUB domains 28 appeared to block the cleavage of the stringlike structure on endothelial cells, suggesting that the CUB domains may directly participate in binding or recognition of VWF under flow. Although the parallel-flow chamber assay may mimic physiological condition, its complexity involving live endothelial cells, histamine stimulation, and platelets makes the quantitation less accurate and kinetic determination of ADAMTS13 and VWF interaction impossible.In the present study, we have developed a simple flow assay based on mechanical-induced shear stress on a mini vortexer or a laminar flow in a BIAcore (Uppsala, Sweden) system to determine the role of the C-terminal ADAMTS13 in recognition and cleavage of multimeric VWF. Our data demonstrate directly and quantitatively that the cooperative activity between the middle C-terminal TSP1 repeats and the distal C-terminal CUB domains of ADAMTS13 may be crucial for productive binding and cleavage of VWF under flow. Materials and methodsThe human study has been approved by the Institutional Re...

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Section: Cleavage Of Vwf By Adamts13 and Variants Under Flowmentioning

confidence: 99%

The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow

Zhang

Pan

Rux

et al. 2007

Blood

109

151

View full text Add to dashboard Cite

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“…The shear force is directly related to the flow rate and inversely related to the third power of the luminal diameter and contributes to determining plaque rupture and thrombus growth (54). This force acts tangentially on the interface of plaque components with different degrees of compliance, thus favoring the sliding of the fibrous cap over the lipidicnecrotic core (55).…”

Section: Physical Forces Acting On Fibrous Capmentioning

confidence: 99%

Role of Inflammation in Atherosclerosis

Spagnoli

Bonanno²,

Sangiorgi³

et al. 2007

Journal of Nuclear Medicine

236

139

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Inflammation plays a major role in all phases of atherosclerosis. Stable plaques are characterized by a chronic inflammatory infiltrate, whereas vulnerable and ruptured plaques are characterized by an ''active'' inflammation involved in the thinning of the fibrous cap, predisposing the plaque to rupture. Although a single vulnerable atherosclerotic plaque rupture may cause the event, there are many other types of plaques, several of which are vulnerable. The existence of multiple types of vulnerable plaques suggests that atherosclerosis is a diffuse inflammatory process. A current challenge is to identify morphologic and molecular markers able to discriminate stable plaques from vulnerable ones, allowing the stratification of patients at high risk for acute cardiovascular and cerebrovascular events before clinical syndromes develop. With that aim in mind, this article summarizes the natural history of atherosclerotic plaques, focusing on molecular mechanisms affecting plaque progression and serum markers correlated with plaque inflammation.

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“…[1][2][3] Red blood cell damage has been reported for WSS values in range of 120-300 (dyne/cm 2 ). [4][5][6] On the other hand, recirculation regions associated with lower WSS and high residence time (RT), in combination with previous exposure to high shear stress, may also increase the risk of thrombus formation. 7,8 Many prior studies report WSS as an important parameter for comparison of different anatomies and clinical scenarios.…”

Section: Introductionmentioning

confidence: 99%

A non-discrete method for computation of residence time in fluid mechanics simulations

2013

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Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not yet fully understood, recent findings suggest that thrombosis risk is increased in regions of flow recirculation and high residence time (RT). Current approaches for calculating RT are typically based on releasing a finite number of Lagrangian particles into the flow field and calculating RT by tracking their positions. However, special care must be taken to achieve temporal and spatial convergence, often requiring repeated simulations. In this work, we introduce a non-discrete method in which RT is calculated in an Eulerian framework using the advection-diffusion equation. We first present the formulation for calculating residence time in a given region of interest using two alternate definitions. The physical significance and sensitivity of the two measures of RT are discussed and their mathematical relation is established. An extension to a point-wise value is also presented. The methods presented here are then applied in a 2D cavity and two representative clinical scenarios, involving shunt placement for single ventricle heart defects and Kawasaki disease. In the second case study, we explored the relationship between RT and wall shear stress, a parameter of particular importance in cardiovascular disease. C 2013 AIP Publishing LLC. [http://dx

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Mechanical factors affecting hemostasis and thrombosis

Cited by 143 publications

References 20 publications

The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow

The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow

Role of Inflammation in Atherosclerosis

A non-discrete method for computation of residence time in fluid mechanics simulations

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