Capillary Microscopic and Rheological Dimensions for the Diagnosis of von Willebrand Disease in Comparison with other Hemorrhagic Diatheses

Koscielny, Jürgen; Latza, Reinhard; Mürsdorf, Stefan; Mrowietz, C.; Kiesewetter, H.; Wenzel, E.; Jung, F.

doi:10.1007/978-3-642-59383-3_14

Cited by 14 publications

(4 citation statements)

References 23 publications

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“…20 Abnormalities in the nail-fold capillary bed of VWD patients include morphological changes with increased dilatation, microscopic bleeding, and torquing (dysplasia). [48][49][50] In this study, we present a plausible hypothesis for the link between increased angiogenesis, vascular malformations and VWD. We show that a lack of VWF results in increased vascularization, suggesting that VWF is required to control the formation of the vascular network.…”

Section: Discussionmentioning

confidence: 90%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

419

285

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The regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to cancer. A poorly understood clinical manifestation of pathological angiogenesis is angiodysplasia, vascular malformations that cause severe gastrointestinal bleeding. Angiodysplasia can be associated with von Willebrand disease (VWD), the most common bleeding disorder in man. VWD is caused by a defect or deficiency in von Willebrand factor (VWF), a glycoprotein essential for normal hemostasis that is involved in inflammation. We hypothesized that VWF regulates angiogenesis. Inhibition of VWF expression by short interfering RNA (siRNA) in endothelial cells (ECs) caused increased in vitro angiogenesis and increased vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2)-dependent proliferation and migration, coupled to decreased integrin ␣v␤3 levels and increased angiopoietin (Ang)-2 release. ECs expanded from blood- IntroductionAngiogenesis, the formation of new vessels from pre-existing ones, occurs physiologically in specific circumstances such as wound healing and the menstrual cycle. Dysregulated angiogenesis contributes to the pathogenesis of many disorders, including diabetes, cancer, and macular degeneration (reviewed in Carmeliet 1 ). Angiogenic factors such as vascular endothelial growth factor (VEGF) and the angiopoietins (Ang) orchestrate signaling pathways that promote endothelial cell (EC) migration, proliferation, and ultimately the formation of a new vessel. VEGF-A is a major regulator of angiogenesis (reviewed in Grothey and Galanis 2 ) and acts on ECs mainly through VEGF receptor-2 (VEGFR-2), a tyrosine kinase receptor (reviewed in Olsson 3 ), to promote endothelial proliferation, migration, and sprouting of tip cells in the early stages of angiogenesis (reviewed in Gerhardt 4 ). Ang-1 and Ang-2, which bind to the endothelial Tie-2 receptor, act in the later stages of blood vessel formation and are essential for the maturation of a stable vascular network and for the maintenance of endothelial integrity (reviewed in Thomas and Augustin 5 ). Ang-1 and Ang-2 were originally identified as agonist and antagonist of Tie-2 signaling, respectively, with Ang-1 supporting EC survival and endothelial integrity 6 and Ang-2 promoting blood vessel destabilization and regression. 7 However, recent data suggest a more complex picture that includes cross-talk between the VEGF and the Ang pathways. 8 Growth factor signaling pathways are influenced by surface adhesion molecules that mediate cell-cell or cell-matrix interactions, particularly by members of the integrin superfamily. The integrin that has received most attention in ECs is ␣v␤3 (reviewed in Hodivala-Dilke 9 ), which mediates binding to several extracellular matrix proteins and growth factor receptors including VEGFR-2, thus influencing VEGFR-2 signaling (reviewed in Somanath et al 10 ). ␣v␤3 plays a complex role in angiogenesis. Although the origina...

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Section: Discussionmentioning

confidence: 90%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

419

285

View full text Add to dashboard Cite

show abstract

“…Whether a selective decrease of the HMWMs of vWF as seen in CF LVAD subjects can cause a similar effect is unknown and warrants investigation. It is also important to note that 10% of patients with congenital vWD develop AVMs (24,25). When considered together, these are intriguing findings and, contrary to the proposed paradigm, may imply that vWD is not only the second hit but also causal in AVM formation.…”

Section: Mechanism Of Ang-2 Productionmentioning

confidence: 91%

Bleeding in continuous flow left ventricular assist device recipients: an acquired vasculopathy?

Patel¹,

Vukelic²,

Jorde³

2016

J. Thorac. Dis.

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“…As VWF is expressed in a mosaic pattern in vascular beds [ 12 ], its contribution to angiogenesis and wound healing may be variable across tissues [ 13 ]. Whether our observation of impaired wound healing can apply to other tissues than the GI tract deserves further clinical studies since microvascular abnormalities have been previously reported in the nail fold and the skin capillary beds of patients with VWD [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 95%