Von Willebrand factor and angiogenesis: basic and applied issues

  title={Von Willebrand factor and angiogenesis: basic and applied issues},
  author={Anna M. Randi and Michael Arthur Laffan},
  journal={Journal of Thrombosis and Haemostasis},
  pages={13 - 20}
  • A. RandiM. Laffan
  • Published 1 January 2017
  • Biology, Medicine
  • Journal of Thrombosis and Haemostasis
The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein. VWF was discovered as a key component of hemostasis, capturing platelets at sites of endothelial damage and synthesized in megakaryocytes and endothelial cells (EC). In recent years, novel functions and binding partners have been identified for VWF. The finding that loss of VWF in EC results in enhanced, possibly dysfunctional… 

von Willebrand factor regulation of blood vessel formation.

The evidence showing that VWF is involved in blood vessel formation is reviewed, the role of VWF high-molecular-weight multimers in regulating angiogenesis is discussed, and the value of studies on BOEC is reviewed in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome.

Impact of Von Willebrand Factor on Bacterial Pathogenesis

In vivo studies using mouse models of bacterial infection and zebrafish larvae provided evidence that the interaction between bacteria and VWF promotes bacterial attachment, coagulation, and thrombus formation, and thereby contributes to the pathophysiology of severe infectious diseases such as infective endocarditis and bacterial sepsis.

Age-Associated Increase in Thrombogenicity and Its Correlation with von Willebrand Factor

This review has aimed to discuss the age-related increase in VWF, its potential mechanisms, and associated coagulopathies as probable consequences.

Circulating Angiogenic Mediators in Patients with Moderate and Severe von Willebrand Disease: A Multicentre Cross-Sectional Study.

Plasma levels of angiogenic factors in patients with various types of VWD were investigated to obtain more insight into the pathogenesis of vascular malformations in these patients and it was hypothesized that VWF deficiency leads to increased circulating levels of other WPB components.

A sticky proposition: The endothelial glycocalyx and von Willebrand factor

It is hypothesized that a similar mechanism may be responsible for the basal secretion of endothelial VWF, whereby the EGC mediates the mechanotransduction of physiological shear stress generated by flowing blood, that in turn contributes to the maintenance of physiological plasma VWF levels.

Role of von Willebrand factor in the angiogenesis of lung adenocarcinoma

The role of VWF in LUAD and its regulatory mechanisms are summarized, andGene expression profiles of LUAD tissues indicate that VWF is differentially expressed inLUAD tissues compared to normal tissues.

Von Willebrand factor contribution to pathophysiology outside of von Willebrand disease

Assessment of contribution of elevated levels of VWF to various thrombotic and nonthrombosis pathological conditions in patients with von Willebrand disease and related conditions is discussed.

New therapies for von Willebrand disease.

  • P. Mannucci
  • Medicine
    Hematology. American Society of Hematology. Education Program
  • 2019
Clinical studies have shown that VWF-only products correct not only the primary VWF deficiency but also the secondary FVIII:C deficiency, and the demonstrated efficacy of these products in various clinical situations and in such a hemostasis-challenging context as surgery testifies to the effectiveness and safety of this approach.

New therapies for von Willebrand disease.

Clinical studies have shown that VWF-only products correct not only the primary VWF deficiency but also the secondary FVIII:C deficiency, and the demonstrated efficacy of these products in various clinical situations and in such a hemostasis-challenging context as surgery testifies to the effectiveness and safety of this approach.

von Willebrand factor deficiency leads to impaired blood flow recovery after ischaemia in mice.

It is concluded that VWF facilitates blood flow recovery in mice and hampers both arteriogenesis and angiogenesis in a hindlimb ischaemia model with impaired leukocytes recruitment and decreased pre-existing collateral density in the absence of VWF.



von Willebrand factor: the old, the new and the unknown

An overview of advances concerning the various structural and functional aspects of VWF will be provided, and it has become increasingly clear that VWF is a more all‐round protein than originally thought, given its involvement in several pathologic processes beyond hemostasis.

Endothelial von Willebrand factor regulates angiogenesis.

A new function of VWF is identified in ECs, which confirms VWF as a protein with multiple vascular roles and defines a novel link between hemostasis and angiogenesis.

New concepts in von Willebrand disease.

  • J. Sadler
  • Biology, Medicine
    Annual review of medicine
  • 2005
Crystallographic studies suggest that VWF level is a useful biomarker for the risk of either bleeding or thrombosis and could be incorporated into a comprehensive approach to treat or prevent these adverse events.

von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy.

In the hemostasis laboratory, the measurement ofVWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice.

Deficiency of von Willebrand factor protects mice from ischemic stroke.

This study indicates that VWF is critically involved in cerebral ischemia, and targeted inhibition of the GPIbalpha-VWF pathway might become a promising therapeutic option.

Circulating and progenitor endothelial cells are abnormal in patients with different types of von Willebrand disease and correlate with markers of angiogenesis

CEC are increased in VWD and are associated with the high levels of cytokines involved in angiogenesis (up‐regulation) and EPC are decreased, suggesting down‐regulation of bone marrow‐derived angiogenic in V WD.

Increased metastatic potential of tumor cells in von Willebrand factor‐deficient mice

In vitro adhesion assays revealed that VWF is able to promote a dose‐dependent adhesion of B16‐BL6 cells via its Arg‐Gly‐Asp (RGD) sequence, and suggest thatVWF plays a protective role against tumor cell dissemination in vivo.

Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice

It is concluded that the absence of vWf, as found in severe von Willebrand disease, leads to a defect in Weibel–Palade body formation, which results in decreased P-selectin translocation to the cell surface and reduced leukocyte recruitment in early phases of inflammation.

ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions.

Results suggest that cleavage of EC-derived ULVWF multimers by ADAMTS-13 is a rapid physiologic process that occurs on endothelial cell surfaces.

von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke.

It is reported that deficiency or reduction ofVWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury and suggesting that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke.