New perspectives on von Willebrand factor functions in hemostasis and thrombosis

Mendolicchio, Grazia Loredana; Ruggeri, Zaverio M.

doi:10.1053/j.seminhematol.2004.09.006

Cited by 57 publications

(41 citation statements)

References 77 publications

(85 reference statements)

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“…VWF mediates the adhesion of platelets to sites of vascular injury and protects FVIII from being cleaved by plasma-proteins. The VWF is stored in the Weibel-Palade-bodies of endothelial cells and in the a-granules of platelets [22]. The liberation follows two pathways and 95% of VWF are continuously freed into plasma.…”

Section: Discussionmentioning

confidence: 99%

The influence of vasovagal response on the coagulation system

et al. 2009

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Section: Discussionmentioning

confidence: 99%

The influence of vasovagal response on the coagulation system

et al. 2009

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“…The von Willebrand Factor (VWF) initiated platelet adhesion is a pivotal step for blood clot formation. [1][2][3][4][5][6][7][8][9] VWF is a large multimeric protein mainly secreted by endothelial cells (EC) to both plasma and the extracellular matrix of the subendothelial vessel wall.…”

mentioning

confidence: 99%

Circulating but not immobilized N-deglycosylated von Willebrand factor increases platelet adhesion under flow conditions

et al. 2013

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The role of von Willebrand factor (VWF) as a shear stress activated platelet adhesive has been related to a coiled-elongated shape conformation. The forces dominating this transition have been suggested to be controlled by the proteins polymeric architecture. However, the fact that 20% of VWF molecular weight originates from glycan moieties has so far been neglected in these calculations. In this study, we present a systematic experimental investigation on the role of N-glycosylation for VWF mediated platelet adhesion under flow. A microfluidic flow chamber with a stenotic compartment that allows one to mimic various physiological flow conditions was designed for the efficient analysis of the adhesion spectrum. Surprisingly, we found an increase in platelet adhesion with elevated shear rate, both qualitatively and quantitatively fully conserved when N-deglycosylated VWF (N-deg-VWF) instead of VWF was immobilized in the microfluidic channel. This has been demonstrated consistently over four orders of magnitude in shear rate. In contrast, when N-deg-VWF was added to the supernatant, an increase in adhesion rate by a factor of two was detected compared to the addition of wild-type VWF. It appears that once immobilized, the role of glycans is at least modified if not-as found here for the case of adhesionnegated. These findings strengthen the physical impact of the circulating polymer on shear dependent platelet adhesion events. At present, there is no theoretical explanation for an increase in platelet adhesion to VWF in the absence of its N-glycans. However, our data indicate that the effective solubility of the protein and hence its shape or conformation may be altered by the degree of glycosylation and is therefore a good candidate for modifying the forces required to uncoil this biopolymer. V C 2013 AIP Publishing LLC. [http://dx

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“…(65) This factor is an adhesive protein that prompts onset and progression of thrombus formation on the site of vascular damage by interacting with components of the extracellular matrix and platelets receptors. (66) Recent studies were carried out aiming to correlate VWF plasma level with prognosis of trauma. Yokota et al (65) in a study related two markers, thrombomodulin and the VWF with severe TBI.…”

Section: Markers Of Vascular Injurymentioning

confidence: 99%