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(Stroke. 2000;31:2653.)
© 2000 American Heart Association, Inc.

Original Contributions

Analysis of Endoglin Expression in Normal Brain Tissue and in Cerebral Arteriovenous Malformations

Shunji Matsubara, MD; Annie Bourdeau, PhD; Karel G. terBrugge, MD; Christopher Wallace, MD Michelle Letarte, PhD

From the Division of Neurosurgery (S.M., C.W.) and Department of Diagnostic and Therapeutic Neuroradiology (K.G.tB.), Toronto Western Hospital and University of Toronto; and Cancer and Blood Research Program, Hospital for Sick Children, and Department of Immunology, University of Toronto (S.M., A.B., M.L.), Toronto, Ontario, Canada.

Correspondence to Dr Michelle Letarte, Cancer and Blood Program, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada. E-mail mablab{at}sickkids.on.ca

Background and Purpose—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-ß 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), -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.

Key Words: cerebral arteriovenous malformations • immunohistochemistry • pathology • transforming growth factors

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