title: Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1.
abstract: Endoglin is predominantly expressed on endothelium and is mutated in hereditary hemorrhagic telangiectasia (HHT) type 1 (HHT1). We report the analysis of endoglin in tissues of a newborn (family 2), who died of a cerebral arteriovenous malformation (CAVM), and in a lung specimen surgically resected from a 78-year-old patient (family 5), with a pulmonary AVM (PAVM). The clinically affected father of the newborn revealed a novel mutation that was absent in his parents and was identified as a duplication of exons 3 to 8, by quantitative multiplex polymerase chain reaction. The corresponding mutant protein (116-kd monomer) and the missense mutant protein (80-kd monomer) present in family 5 were detected only as transient intracellular species and were unreactive by Western blot analysis and immunostaining. Normal endoglin (90-kd monomer) was reduced by 50% on peripheral blood-activated monocytes of the HHT1 patients. When analyzed by immunostaining and densitometry, presumed normal blood vessels of the newborn lung and brain and vessels adjacent to the adult PAVM showed a 50% reduction in the endoglin/PECAM-1 ratio. A similar ratio was observed in the CAVM and PAVM, suggesting that all blood vessels of HHT1 patients express reduced endoglin in situ and that AVMs are not attributed to a focal loss of endoglin.
authors.affiliation: Blood and Cancer Research Program, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bourdeau
authors.forename: U
authors.initials: U
authors.lastname: Cymerman
authors.forename: M E
authors.initials: ME
authors.lastname: Paquet
authors.forename: W
authors.initials: W
authors.lastname: Meschino
authors.forename: W C
authors.initials: WC
authors.lastname: McKinnon
authors.forename: A E
authors.initials: AE
authors.lastname: Guttmacher
authors.forename: L
authors.initials: L
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Letarte
mesh_terms: D000368:Aged; D015703:Antigens, CD; D001808:Blood Vessels / Q000002:abnormalities / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000002:abnormalities / Q000378:metabolism; D011956:Receptors, Cell Surface; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA