Analysis of endoglin expression in normal brain tissue and in cerebral arteriovenous malformations.
OBJECTIVE
A high incidence of arteriovenous malformations (AVMs) is associated with hereditary hemorrhagic telangiectasia type 1. Endoglin, the gene mutated in this disorder, is expressed at reduced levels on blood vessels of these patients. Since endoglin is a component of the transforming growth factor-beta receptor complex critical for vascular development and homeostasis, we determined its expression in sporadic cerebral AVMs and in normal brain vessels.


METHODS
Twenty cerebral AVMs and 10 normal brain samples were analyzed for endoglin, platelet endothelial cell adhesion molecule 1 (PECAM-1), alpha-smooth muscle cell actin, vimentin, and desmin by immunohistochemistry.


RESULTS
In normal brain, endoglin was found not only on the endothelium of all vessels but also on the adventitial layer of arteries and arterioles. In cerebral AVMs, the numerous vessels present expressed endoglin on both endothelium and adventitia. Arterialized veins, identified by lack of elastin and uneven thickness of smooth muscle cells, revealed endoglin-positive mesenchymal cells in the adventitia and perivascular connective tissue. These cells were fibroblasts since they expressed vimentin but not actin and/or desmin.


CONCLUSIONS
This is the first report of endoglin expression on adventitia of normal brain arteries and on arterialized veins in cerebral AVMs. Increasing numbers of endoglin-positive endothelial and adventitial cells were seen in sporadic cerebral AVMs, but endoglin density was normal. Thus, it is not involved in the generation of these lesions. However, the presence of endoglin on fibroblasts in the perivascular stroma suggests an active role for this protein in vascular remodeling in response to increased blood flow and shear stress.
Matsubara
S
S
Division of Neurosurgery, Toronto Western Hospital and University of Toronto, Ontario, Canada.
Bourdeau
A
A
terBrugge
K G
KG
Wallace
C
C
Letarte
M
M
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002536:Cerebral Arteries / Q000737:chemistry / Q000378:metabolism; D002550:Cerebral Veins / Q000737:chemistry / Q000378:metabolism; D003893:Desmin / Q000032:analysis / Q000378:metabolism; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D002538:Intracranial Arteriovenous Malformations / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D014746:Vimentin / Q000032:analysis / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D003893:Desmin; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D014746:Vimentin