Gene Microarray Analysis of Human Brain Arteriovenous Malformations.
Hashimoto, Tomoki M.D.; Lawton, Michael T. M.D.; Wen, Gen M.D.; Yang, Guo-Yuan M.D., Ph.D.; Chaly, Thomas Jr. B.S.; Stewart, Campbell L. B.A.; Dressman, Holly K. Ph.D.; Barbaro, Nicholas M. M.D.; Marchuk, Douglas A. Ph.D.; Young, William L. M.D.
54(2):410-425, February 2004.
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OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique.
METHODS: We analyzed BAVM and control brain samples obtained by temporal lobectomy for medically intractable seizure by Affymetrix Human Gene Set U95Av2 (Affymetrix, Inc., Santa Clara, CA). The gene microarray data were compared with new and previously published data that used conventional molecular biology techniques.
RESULTS: We analyzed six BAVM and five control brain samples. From 12,625 gene probes assayed, 1781 gene probes showed differential expression between BAVMs and controls. BAVM samples had a gene expression pattern that was distinct from those of control brain samples. Increased messenger ribonucleic acid expression of vascular endothelial growth factor A was accompanied by increased expression of its protein product. A majority of the gene data was in agreement with previously published data. The gene microarray data generated a new testable hypothesis regarding integrin, and we found increased expression of integrin [alpha]v[beta]3 protein in BAVMs.
CONCLUSION: The gene expression pattern of BAVMs was distinct from those of control brain samples. We verified the gene microarray data by demonstrating that increased gene expression levels for angiogenesis-related molecules were accompanied by increased levels of their protein product expression. The gene microarray technique may be a useful tool to study multiple pathways simultaneously in BAVM specimens.
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