Perlecan Domain V is Upregulated in Human Brain Arteriovenous Malformation (BAVM) and could Mediate VEGF Effect in Lesional Tissue

• Published in: Neuroreport Vol. 23; no. 10; pp. 627 - 630
• Main Authors: Kahle, Michael P., Lee, Boyeon, Pourmohamad, Tony, Cunningham, Austin, Su, Hua, Kim, Helen, Chen, Yongmei, McCulloch, Charles E., Barbaro, Nicholas M., Lawton, Michael T., Young, William L., Bix, Gregory J.
• Format: Journal Article
• Language: English
• Published: 11-07-2012
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/WNR.0b013e3283554c5c

Brain arteriovenous malformation (BAVM), a rare but important cause of intracranial hemorrhage, has increased angiogenesis and inflammation as key components of the nidus of abnormal vessels and stroma that form the resected surgical specimen. Accordingly, vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGFβ) have both been implicated in BAVM pathology for their pro-angiogenic and vascular-regulating roles. The c-terminal fragment of the extracellular matrix component perlecan (domain V, DV) has been shown to be increased and to, via the α5β1 integrin, increase VEGF levels in and around areas of cerebral ischemic injury, another pro-angiogenic condition. We sought to determine whether the concentrations of DV, DV’s proangiogenic receptor α5β1 integrin, or DV’s anti-angiogenic receptor α2β1 integrin are elevated in human BAVM tissue. DV levels were increased in BAVM compared to control brain tissue from epileptic resection, as was α5β1 integrin. Additionally, α5β1 integrin was preferentially increased and localized to endothelial cells compared to α2β1 integrin. VEGF and TGFβ levels were also increased in BAVM compared to control tissue. Furthermore, increases in all components were strongly correlated. Excessive generation of pro-angiogenic DV in BAVM suggests that DV may participate in its pathology and may represent a future therapeutic target.