Angiogenesis and vascular malformations: Antiangiogenic drugs for treatment of gastrointestinal bleeding

Juergen,; Bauditz,; Herbert,; Lochs,

doi:10.3748/wjg.13.5979

Cited by 36 publications

(26 citation statements)

References 39 publications

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“…Recent studies have suggested that angiogenesis is involved in the pathogenesis of vascular malformations. 21 Increased VEGF expression has been reported in human colonic angiodysplasia 22 and, more recently, anti-angiogenic treatments have been cautiously tested to control bleeding from vascular malformations, with promising results (reviewed by Bauditz and Lochs 23 ).…”

Section: Introductionmentioning

confidence: 99%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

426

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: Introductionmentioning

confidence: 99%

Endothelial von Willebrand factor regulates angiogenesis

Starke

Ferraro

Paschalaki

et al. 2011

Blood

426

280

View full text Add to dashboard Cite

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“…Thalidomide treatment of HHT patients was shown to enhance blood vessel stabilization and reduce nosebleed frequency [123]. Moreover, it has been shown that VEGF levels are elevated in skin telangiectatic lesions of HHT patients and that anti-angiogenic drugs, such as thalidomide and bevacizumab (anti-VEGF antibody), are effective in treating gastrointestinal bleedings and liver AVMs, respectively [133][134][135].…”

Section: Perturbation Of Tgf Signaling In Cardiovascular Diseasesmentioning

confidence: 99%

TGFβ Signaling and Cardiovascular Diseases

Pardali¹,

Dijke²

2012

Int. J. Biol. Sci.

155

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Transforming growth factor  (TGF) family members are involved in a wide range of diverse functions and play key roles in embryogenesis, development and tissue homeostasis. Perturbation of TGF signaling may lead to vascular and other diseases. In vitro studies have provided evidence that TGF family members have a wide range of diverse effects on vascular cells, which are highly dependent on cellular context. Consistent with these observations genetic studies in mice and humans showed that TGF family members have ambiguous effects on the function of the cardiovascular system. In this review we discuss the recent advances on TGF signaling in (cardio)vascular diseases, and describe the value of TGF signaling as both a disease marker and therapeutic target for (cardio)vascular diseases.

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“…For patients without coagulopathy and multiple vascular intestinal malformations who present with recurrent, intractable GI bleeding, varying degrees of success have been achieved with hormonal treatment, somatostatin and antiangiogenic treatment [1,4,5]. In our patient's case, hormonal treatment with danazol was transiently successful at decreasing the frequency of bleeding, but medication compliance was poor.…”

Section: Discussionmentioning

confidence: 71%