Endoglin (CD105) and endothelial nitric oxide synthase (eNOS) assist in regulating vascular development. Variation in expression of these factors is linked to errors in vascular growth and remodeling in invasive lesions.
To clarify the role of endoglin and eNOS in the growth of extracranial head and neck arteriovenous malformations (AVMs), an invasive and high-flow vascular anomaly.
Immunohistochemistry and Western blot study at an academic research center.
Frozen and formalin-fixed paraffin-processed human AVMs (n = 14) were examined for expression of CD105 and eNOS. Expression in infantile hemangiomas (n = 9) and in normal skin with subcutaneous tissue (n = 9) was used for comparison.
Quantitative assessment and localization of CD105 and eNOS protein expression were performed on each specimen by immunohistochemistry and Western blot analysis. Protein expression levels were compared with β-actin level and were semiquantitatively assessed.
Abundant CD105 protein was found in AVMs but was not present in infantile hemangiomas or normal skin with subcutaneous tissue. Expression of eNOS protein in AVMs and infantile hemangiomas was similar (P = .20) and was significantly greater than that in normal skin with subcutaneous tissue (P < .001 and P = .008, respectively). Immunohistochemistry demonstrated that CD105 and eNOS are predominantly located in AVM vascular endothelial cells.
CD105 and eNOS are present and significantly expressed in head and neck AVMs. Expression of CD105 and eNOS may have an important role in the angiogenesis and vascular remodeling of AVMs. CD105 can be used as a specific marker for AVM endothelial cells.
"With time, AVMs will expand to excessive size and infiltrate local tissues. This relentless growth will cause mass effect on surrounding tissues, lead to functional deficits, aesthetic impairment, long-term sequelae and even become a life-threatening problem [6,7,11]. Unfortunately, current therapeutic modalities are unsatisfied; especially many treatments have shown to stimulate the AVMs recruitment [6,7]. "
[Show abstract][Hide abstract] ABSTRACT: Arteriovenous malformations (AVMs) are a type of high-flow vascular malformations that most commonly occurs in the head and neck. They are present at birth but are usually clinically asymptomatic until later in life. The pathogenesis of AVMs remains unclear and therapeutic approaches to AVMs are unsatisfied. In order to provide a tool for studying the pathogenesis and therapies of this disease, we established and studied a xenograft animal model of human AVMs.
Fresh human AVMs specimens harvested from 4 patients were sectioned (5x5x5 mm) and xenografted subcutaneously in 5 immunologically naive nude mice (Athymic Nude-Foxn1nu). Each mouse had four pieces specimens in four quadrants along the back. The grafts were observed weekly for volume, color and texture. The grafts were harvested at every 30 days intervals for histologic examination. All grafts (n = 20) were sectioned and stained for hematoxylin and eosin (H&E). Comparative pathologic evaluation of the grafts and native AVMs were performed by two blinded pathologists. Immunohistochemical examination of human-specific nuclear antigen, vascular endothelial growth factor receptor-2 (VEGFR-2) and Ki-67 was performed.
Clinical characteristics and pathologic diagnosis of native human derived AVMs were confirmed. 85% (n = 17) of AVM xenografts survived although the sizes decreased after implantation. Histological examination demonstrated numerous small and medium-size vessels and revealed structural characteristics matching the native AVMs tissue.76.5% (n = 13) of the surviving xenografts were positive for Ki-67 and human-specific nuclear antigen suggesting survival of the human derived tissue, 52.9% (n = 9) were positive for VEGFR-2.
This preliminary xenograft animal model suggests that AVMs can survive in the nude mouse. The presence of human-specific nuclear antigen, VEGFR-2, and Ki-67 demonstrates the stability of native tissue qualities within the xenografts.
[Show abstract][Hide abstract] ABSTRACT: Arteriovenous malformations (AVMs) are fast-flow vascular malformations composed of a complex vessel network directly connecting feeding arteries to draining veins. The intervening normal capillary network is absent. Proper diagnosis and treatment of AVMs is challenging and in need of an interdisciplinary team of experienced physicians. Careful analysis of the clinical features and evaluation of therapeutic options represent the basis for successful management of AVMs. This article will focus on the clinical and radiological findings and in particular on interdisciplinary management strategies of AVMs including minimally invasive endovascular and surgical treatment.
Seminars in Pediatric Surgery 08/2014; 23(4). DOI:10.1053/j.sempedsurg.2014.07.005 · 2.22 Impact Factor
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