title: Tie endothelial cell-specific receptor tyrosine kinase is upregulated in the vasculature of arteriovenous malformations.
abstract: Arteriovenous malformations (AVMs) are congenital lesions composed of abnormal vasculature, with no capillary component, and are clinically significant due to their tendency to spontaneously hemorrhage. The mechanisms regulating the genesis and progression of these lesions are unknown. In order to study the role of angiogenesis in AVMs, we have analyzed the expression of the endothelial cell mitogen vascular endothelial growth factor (VEGF) and a novel endothelial cell-specific receptor tyrosine kinase, Tie, by in situ hybridization and immunohistochemistry in these malformations and surrounding brain tissue. We have previously shown upregulation of Tie accompanying wound healing and tumor progression. In this study, we demonstrate significantly elevated levels of Tie mRNA and protein in AVM and surrounding brain vasculature. Upregulation of VEGF mRNA was observed in the cells of brain parenchyma adjacent to the AVM, and VEGF protein was detected in this tissue as well as in AVM endothelia. Normal brain, in comparison, expressed little or no Tie or VEGF. The significant upregulation of VEGF and Tie in AVMs may indicate some ongoing angiogenesis, possibly contributing to the slow growth and maintenance of the AVM, and could be of potential use in the therapeutic targeting of these lesions.
authors.affiliation: Neurobiology Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Hatva
authors.forename: J
authors.initials: J
authors.lastname: Jääskeläinen
authors.forename: H
authors.initials: H
authors.lastname: Hirvonen
authors.forename: K
authors.initials: K
authors.lastname: Alitalo
authors.forename: M
authors.initials: M
authors.lastname: Haltia
mesh_terms: D000328:Adult; D034961:Antigens, Nuclear; D015415:Biomarkers; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002648:Child; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D042764:Receptors, TIE; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D034961:Antigens, Nuclear; D015415:Biomarkers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042764:Receptors, TIE