Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations.
OBJECTIVE
To further understand the role of angiogenic growth factors in the development of cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs), we investigated endothelial cell (EC) expression of receptors for vascular endothelial growth factor (VEGF) and angiopoietin systems in patients with surgically resected lesions.


METHODS
Paraffin-embedded sections of five AVMs, CCMs, and normal control brain tissue samples were stained immunohistochemically with antibodies to von Willebrand factor and CD31 (to characterize ECs) and angiogenesis growth factor receptors Flt-1 (VEGF-R1), Flk-1 (VEGF-R2), Tie-1, and Tie-2. We counted large and small vessels in each specimen, assessed each specimen's immunoexpression of each antigen, and analyzed differences between CCMs, AVMs, and the normal control brain tissue samples.


RESULTS
The ECs of CCMs, AVMs, and normal control brain tissue samples expressed the von Willebrand factor uniformly, but the ECs of CCMs were largely negative for CD31 (P < 0.05). Flk-1, Flt-1, and Tie-2 were not expressed in the control brain tissue samples. The proportion of immunopositive vessels to VEGF receptors Flk-1 and Flt-1 was significantly greater in AVMs and CCMs than in the control brain tissue samples (P < 0.05). Tie-2 in AVMs and CCMs was expressed in a higher percentage of immunopositive vessels than in the control brain tissue samples, but the difference was not statistically significant. Tie-1 was expressed in rare vessels of all lesion types and control brain tissue samples.


CONCLUSIONS
ECs of CCMs do not seem to express CD31 to the same extent that AVMs and normal brain tissue do. AVMs and CCMs show greater expression of VEGF receptors, but not of angiopoietin receptors, than normal brain tissue does.
Uranishi
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R
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Baev
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Ng
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Kim
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JH
Awad
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D000293:Adolescent; D000328:Adult; D000368:Aged; D002426:Cavernous Sinus / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D002648:Child; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D012016:Reference Values; D040281:Vascular Endothelial Growth Factor Receptor-1; D014841:von Willebrand Factor / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D014841:von Willebrand Factor; C501162:FLT1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1