Active Angiogenesis in an Extensive Arteriovenous Vascular Malformation

Redondo, Pedro; Martínez-Cuesta, Antonio; Quetglas, Emilio García; Idoate, M.

doi:10.1001/archderm.143.8.1043

Cited by 17 publications

(9 citation statements)

References 5 publications

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“…Indeed, increased levels of Ang-2 have been reported in patients with arteriovenous malformations. 47 Increased Ang-2 levels could also explain, at least in part, the reduced levels of integrin ␣v␤3 in VWF-deficient cells: in a recent paper by Thomas et al, Ang-2 was shown to induce ␣v␤3 internalization and degradation in ECs. 34 Based on these results, we propose that VWF modulates angiogenesis by regulating Ang-2 storage in ECs, thus indirectly influencing VEGFR-2 signaling and ␤3-integrin trafficking.…”

Section: Discussionmentioning

confidence: 99%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

415

280

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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: 99%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

415

280

View full text Add to dashboard Cite

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“…In mice and humans, Ang‐2 is selectively expressed in ovary, uterus and placenta and as an angiogenic switch in tumorigenesis, while Ang‐1 is widely expressed in both the embryo and the adult 8 . We previously reported elevated Ang‐2, TIE‐2 and VEGF levels in the serum of a patient with extensive arteriovenous malformation 9 …”

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confidence: 98%

Angiogenic and prothrombotic markers in extensive slow-flow vascular malformations: implications for antiangiogenic/antithrombotic strategies

Redondo¹,

Aguado²,

Marquina³

et al. 2009

British Journal of Dermatology

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“…However, hypothetically the vasoproliferative foci in AVM may undergo a similar pattern of maturation as seen in other benign vascular lesions, and hence contribute to the hamartomatous mass of vessels and associated matrix tissue that is characteristic for AVM 9 . Such a feature could explain the episodes of disproportionate growth that have been described in AVM 10,11 . We investigated 15 vascular malformations in comparison to 8 IHs and 5 PGs which were histopathologically screened for the presence of vasoproliferative foci as well as conglomerates of maturated microvessels, using the same histomorphological criteria in all lesions.…”

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confidence: 99%