Perlecan domain V is upregulated in human brain arteriovenous malformation and could mediate the vascular endothelial growth factor effect in lesional tissue.
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, both vascular endothelial growth factor (VEGF) and transforming growth factor-β have been implicated in the pathology of BAVM for their proangiogenic and vascular-regulating roles. The C-terminal fragment of the extracellular matrix component perlecan (domain V, DV) has been shown to be increased and through the α5β1 integrin, to increase VEGF levels in and around areas of cerebral ischemic injury, another proangiogenic condition. We aimed to determine whether the concentrations of DV, DV's proangiogenic receptor α5β1 integrin, or DV's antiangiogenic receptor α2β1 integrin are elevated in human BAVM tissue. DV levels were increased in BAVM compared with control brain tissue from epileptic resection, as was α5β1 integrin. In addition, α5β1 integrin was preferentially increased and localized to endothelial cells compared with α2β1 integrin. VEGF and transforming growth factor-β levels were also increased in BAVM compared with control tissue. Furthermore, increases in all components were strongly correlated. Excessive generation of proangiogenic DV in BAVM suggests that DV may participate in its pathology and may represent a future therapeutic target.
Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, College Station, Texas 77843, USA.
Michael P
MP
Kahle
Boyeon
B
Lee
Tony
T
Pourmohamad
Austin
A
Cunningham
Hua
H
Su
Helen
H
Kim
Yongmei
Y
Chen
Charles E
CE
McCulloch
Nicholas M
NM
Barbaro
Michael T
MT
Lawton
William L
WL
Young
Gregory J
GJ
Bix
D000328:Adult; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017434:Protein Structure, Tertiary / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000502:physiology; D055815:Young Adult
D019812:Heparan Sulfate Proteoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C071927:perlecan