Abnormal Pattern of Tie-2 and Vascular Endothelial Growth Factor Receptor Expression in Human Cerebral Arteriovenous Malformations

Hashimoto, Tomoki; Emala, Charles W.; Joshi, Shailendra; Mesa-Tejada, Ricardo; Quick, Christopher M.; Feng, Lei; Libow, Adam D.; Marchuk, Douglas A.; Young, William L.

doi:10.1097/00006123-200010000-00022

Cited by 115 publications

(70 citation statements)

References 32 publications

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“…19,20,22 Studies of AVM tissue have shown increased endothelial cell proliferation and increased expression of angiopoietin-2 and vascular endothelial growth factor, which promote vascular destabilization and proliferation, respectively. 17 However, the exact triggering event that leads to increased and disorganized angiogenesis ultimately leading to AVM formation has not been identified. Mice with ALK1 deficiency develop de novo AVMs after angiogenic stimulation.…”

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Are parenchymal AVMs congenital lesions?

Morales-Valero

Bortolotti

Sturiale

et al. 2014

FOC

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A long-held dogma in neurosurgery is that parenchymal arteriovenous malformations (AVMs) are congenital. However, there is no strong evidence supporting this theory. An increasing number of documented cases of de novo formation of parenchymal AVMs cast doubt on their congenital nature and suggest that indeed the majority of these lesions may form after birth. Further evidence suggesting the postnatal development of parenchymal AVMs comes from the exceedingly rare diagnosis of these lesions in utero despite the widespread availability of high-resolution imaging modalities such as ultrasound and fetal MRI. The exact mechanism of AVM formation has yet to be elucidated, but most likely involves genetic susceptibility and environmental triggering factors. In this review, the authors report 2 cases of de novo AVM formation and analyze the evidence suggesting that they represent an acquired condition.

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confidence: 99%

Are parenchymal AVMs congenital lesions?

Morales-Valero

Bortolotti

Sturiale

et al. 2014

FOC

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“…143 In brain AVMs, intranidal vessels are exposed to abnormally high blood flow that creates high shearing forces, which can similarly activate shearinduced genes. 40 Takagi and colleagues have shown that phosphorylated ERK is upregulated in the SMCs of the media layer in brain AVMs. The activation of this pathway signals SMC proliferation, which contributes to the vascular remodeling and growth/regression of these lesions.…”

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Cerebral arteriovenous malformations. Part 1: cellular and molecular biology

Moftakhar

Hauptman

Malkasian

et al. 2009

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Object The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression—and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs. Methods A comprehensive literature review was conducted using PubMed to reveal the molecular biology of AVMs as it relates to their complex growth and behavior patterns. Results Growth factors involved in AVMs include vascular endothelial growth factor, fibroblast growth factor, transforming growth factor β, angiopoietins, fibronectin, laminin, integrin, and matrix metalloproteinases. Conclusions Understanding the complicated molecular milieu of developing AVMs is essential for defining their natural history. Growth factors, extracellular matrix proteins, and other molecular markers will be the key to unlocking novel targeted drug treatments for these brain malformations.

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“…6,8,47,48 Investigators have suggested that abnormal angiogenesis may play a central role in AVM formation and progression and have indicated that vascular remodeling may be mediated by angiogenic factors. 12,20,52 In particular, vascular endothelial growth factor (VEGF), a potent endothelial cell mitogen, is thought to play a key role. Increased VEGF expression has been demonstrated in the endothelium, subendothelium, and adventitia of resected AVM specimens.…”

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Plasma Levels of Vascular Endothelial Growth Factor After Treatment for Cerebral Arteriovenous Malformations

Kim

Hahn

Kellner

et al. 2008

Stroke

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Background and Purpose— The role of abnormal angiogenesis in the formation and progression of cerebral arteriovenous malformations (AVMs) is unclear. Previous studies have demonstrated increased local expression of vascular endothelial growth factor (VEGF) in AVM tissue and increased circulating levels of VEGF in AVM patients. We sought to further investigate the role of VEGF in AVM pathophysiology by examining changes in plasma VEGF levels in patients undergoing treatment for AVMs. Methods— Three serial blood samples were obtained from 13 AVM patients undergoing treatment: (1) before any treatment, (2) 24 hours postresection, and (3) 30 days postresection. Plasma VEGF concentrations were measured via commercially available enzyme-linked immunosorbent assay (ELISA). For controls, blood samples were obtained from 29 lumbar laminectomy patients. Results— The mean plasma VEGF level in AVM patients at baseline was 36.08±13.02 pg/mL, significantly lower than that of the control group (80.52±14.02 pg/mL, P =0.028). Twenty-four hours postresection, plasma VEGF levels dropped to 20.09±4.54 pg/mL, then increased to 66.81±26.45 pg/mL 30 days later ( P =0.048). The mean plasma VEGF concentration 30 days after resection was no longer significantly different from the control group ( P =0.33). Conclusions— Plasma VEGF levels in 13 AVM patients were unexpectedly lower than controls, dropped early after AVM resection, then significantly increased 30 days later. These results support the key role of abnormal angiogenesis in AVM pathophysiology and suggest that a disruption in systemic VEGF expression may contribute to the natural history of these lesions.

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Abnormal Pattern of Tie-2 and Vascular Endothelial Growth Factor Receptor Expression in Human Cerebral Arteriovenous Malformations

Abstract: AVM vessels exhibited abnormal expression of Tie-2 and VEGF-Rs, both of which may contribute to the pathogenesis of AVMs.

Cited by 115 publications

References 32 publications

Are parenchymal AVMs congenital lesions?

Are parenchymal AVMs congenital lesions?

Cerebral arteriovenous malformations. Part 1: cellular and molecular biology

Plasma Levels of Vascular Endothelial Growth Factor After Treatment for Cerebral Arteriovenous Malformations

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