Update on von Willebrand factor multimers

Stockschlaeder, Marcus; Schneppenheim, Reinhard; Budde, Ulrich

doi:10.1097/mbc.0000000000000065

Cited by 176 publications

(85 citation statements)

References 119 publications

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“…13B; indicated by G) (Robertson et al, 2003). The von Willebrand factor (vWF, in particular von Willebrand factor A (vWFA)) in vascular tissues acts as a mechanosensor that responds to shear stress through proportional multimerization to induce distinct interactions with different protein interactors (Stockschlaeder et al, 2014). …”

Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

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Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Carreon

Merwe

Fellman

et al. 2017

Progress in Retinal and Eye Research

227

196

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In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm’s canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins.

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Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

“…Our goal is to depict an analogy between vWF and cochlin multimerization in response to shear stress or mechanical stretching. Detailed descriptions of multimer variants and disease association can be found elsewhere (Stockschlaeder et al, 2014). …”

Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Carreon

Merwe

Fellman

et al. 2017

Progress in Retinal and Eye Research

227

196

View full text Add to dashboard Cite

show abstract

“…Although the eye has a substantially lower fluid flow rate than either of these systems, similar mechanotransducing molecules are present in these different systems. An important factor for mechanosensing in the hemodynamic system is von Willebrand factor A (vWFA), a mechanosensor that senses shear stress allowing for various protein interactions to initiate or take place (Stockschlaeder et al, 2014). Cochlin has two distinct von Willebrand Factor A-like (vWFA) domains (Bhattacharya et al, 2005b; Bhattacharya, 2006).…”

Section: Extracellular Matrix Changes Attributing To Segmental Outmentioning

confidence: 99%

Segmental outflow of aqueous humor in mouse and human

Carreon

Edwards

Wang

et al. 2017

Experimental Eye Research

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The main and only modifiable risk factor in glaucoma, the group of usually late onset progressive and irreversible blinding optic neuropathies, is elevated intraocular pressure (IOP). The increase in IOP is due to impeded aqueous humor (AH) outflow through the conventional pathway. The aberrant increased resistance at the trabecular meshwork (TM), the filter-like region in the anterior eye chamber is the major contributory factor in causing the impeded outflow. In normal as well as in glaucoma eyes the regions of the TM are divided into areas of high and low flow. The collector channels and distal outflow regions are now increasingly being recognized as potential players in contributing to impede AH outflow. Structural and molecular make-up contributing to the segmental blockage to outflow is likely to provide greater insight. Establishing segmental blockage to outflow in model systems of glaucoma such as the mouse in parallel to human eyes will expand our repertoire of tools for investigation. Further study into this area of interest has the potential to ultimately lead to the development of new therapeutics focused on lowering IOP by targeting the various components of segmental blockage of outflow in the TM and in the distal outflow region.

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“…It affects approximately one in 10,000 individuals sufficiently to be referred to a tertiary care centre. 1 von Willebrand factor (VWF) is a very large multimeric glycoprotein 2 that performs two essential haemostatic functions; it provides a means to bind platelets at sites of vascular damage and at high shear stress supports platelet aggregation. It also carries and protects coagulation factor VIII (FVIII) in the circulation, delivering it to sites of vascular injury.…”

Section: Introductionmentioning

confidence: 99%

Diagnosing von Willebrand disease: genetic analysis

Goodeve

2016

Hematology

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Investigation of a patient with possible von Willebrand disease includes a range of phenotypic analyses. Often, this is sufficient to discern disease type, and this will suggest relevant treatment. However, for some patients, phenotypic analysis does not sufficiently explain the patient’s disorder and for this group, genetic analysis can aid diagnosis of disease type. PCR and Sanger sequencing have been mainstays of genetic analysis for several years. More recently, next generation sequencing has become available, with the advantage that several genes can be simultaneously analysed where necessary, e.g. for discrimination of possible type 2N von Willebrand disease or mild haemophilia A. Additionally, several techniques can now identify deletions/duplications of an exon or more that result in von Willebrand disease including multiplex ligation-dependent probe amplification and micro-array analysis. Algorithms based on next generation sequencing data can also identify missing or duplicated regions. These newer techniques enable causative VWF defects to be identified in more patients than previously, aiding a specific VWD diagnosis. Genetic analysis can also be helpful in the discrimination between type 2B and platelet-type von Willebrand disease and in prenatal diagnosis for families with type 3.

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Update on von Willebrand factor multimers

Cited by 176 publications

References 119 publications

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Segmental outflow of aqueous humor in mouse and human

Diagnosing von Willebrand disease: genetic analysis

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