Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1

Am J Pathol. 2000 Mar;156(3):911-23. doi: 10.1016/S0002-9440(10)64960-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD
  • Blood Vessels / abnormalities
  • Blood Vessels / metabolism*
  • Blotting, Western
  • Cells, Cultured
  • DNA / analysis
  • DNA Mutational Analysis
  • Endoglin
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Infant, Newborn
  • Intracranial Arteriovenous Malformations / metabolism*
  • Lung / blood supply
  • Lung / pathology
  • Male
  • Monocytes / metabolism
  • Mutation, Missense
  • Pedigree
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polymerase Chain Reaction
  • Pulmonary Artery / abnormalities
  • Pulmonary Artery / metabolism
  • Receptors, Cell Surface
  • Telangiectasia, Hereditary Hemorrhagic / genetics
  • Telangiectasia, Hereditary Hemorrhagic / metabolism*
  • Umbilical Veins / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Cell Surface
  • Vascular Cell Adhesion Molecule-1
  • DNA