Expression of Transforming Growth Factor-β Complex in Arteriovenous Malformations
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概要
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The factors responsible for the development of cerebral arteriovenous malformations (AVMs) are not well known. Patients with hereditary hemorrhagic telangiectasia (HHT) have cutaneous vascular dys-plasia and a high propensity to develop systemic and cerebral AVMs. Transforming growth factor-β (TGF-β) complex has been implicated in HHT. The aim of this study was to evaluate the expression of TGF-β1, TGF-β2, TGF-β3, and their two receptors (R1 and R2) in AVMs and in normal brain vessels. Formalin-fixed, paraffin-embedded tissues from 20 patients with cerebral AVMs (including two patients with HHT) were sequentially sectioned into 6μm sections. Similar sections from normal brain tissue were obtained from five patients without AVMs and no intracranial pathology, who had died from unrelated causes. The normal tissue sections included large intracranial arteries, small arteries, venous sinuses, cortical veins, and brain tissue containing arterioles, capillaries, and venules. All speci-mens underwent immunohistochemical analyses with polyclonal antibodies to the following antigens: TGF-β1, TGF-β2, TGF-β3, and R1 and R2. The immunoreactivity, when present, was consistently noted in endothelial cells and in the medial smooth muscle. The intensity of vessel wall immunostaining was graded on a scale from 0 to 3. The mean staining grades of normal vessels for TGF-β1, TGF-β2, TGF-β3, R1, and R2 were 0.6 (range 0-1), 3, 2.8 (range 2-3), 1.6 (range 0-2), and 3, respectively, whereas the mean staining grades of AVM vessels were 0.3 (range 0-1), 0.8 (range 0-1), 0.6 (range 0-1), 1.4 (range 0-2), and 0.9 (range 0-1), respectively. The study thus demonstrated that normal brain vessels (arteries, veins, small vessels) have strong (range 2.8-3) immunostaining for TGF-β2, TGF-β3, and R2, and that the AVM nidus vessels have a paucity (range 0.8-0.9) of staining for these factors. In AVM vessels that had zero immunoreactivity to the above three factors, the vessel wall was fibrocollagenous rather than muscular. Further studies to examine the TGF-β complex behavior in AVMs are needed.
- 社団法人 日本脳神経外科学会の論文
著者
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Yang Xiao
Department Of Advanced Materials Science Graduate School Of Frontier Sciences The University Of Toky
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REMPEL Sandra
Departments of Neurosurgery, Henry Ford Hospital
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MALIK Ghaus
Departments of Neurosurgery, Henry Ford Hospital
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ABDULRAUF Saleem
Departments of Neurosurgery, Henry Ford Hospital
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GUTIERREZ Jorge
Departments of Pathology, Henry Ford Hospital
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YANG Xiao
Departments of Neurosurgery, Henry Ford Hospital
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