Analysis of endoglin expression in normal brain tissue and in cerebral arteriovenous malformations

Background and Purpose-A high incidence of arteriovenous malformations (AVM s) is associated with hereditary hemorrhagic telangiectasia type 1. Endogli n, the gene mutated in this disorder, is expressed at reduced levels on blo od vessels of these patients. Since endoglin is a component of the transfor ming 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 -s mooth 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. I n cerebral AVMs, the numerous vessels present expressed endoglin on both en dothelium and adventitia. Arterialized veins, identified by lack of elastin and uneven thickness of smooth muscle cells, revealed endoglin-positive me senchymal 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 o f normal brain arteries and on arterialized veins in cerebral AVMs. Increas ing numbers of endoglin-positive endothelial and adventitial cells were see n in sporadic cerebral AVMs, but endoglin density was normal. Thus, it is n ot involved in the generation of these lesions. However, the presence of en doglin on Fibroblasts in the perivascular stroma suggests an active role fo r this protein in vascular remodeling in response to increased blood flow a nd shear stress.