To explore the molecular basis underlying beta-amyloid peptide (A beta)-induced toxicity in the cerebrovasculature, we performed a cDNA microarray analysis to investigate the transcriptional profile induced by A beta in human brain microvascular endothelial cells (HBMECs). This study identified 24 differentially expressed genes in HBMECs upon A beta treatment. Among these genes, we found that the gene for a well-characterized calcium-regulating hormone, stanniocalcin-1 (STC1) was specifically up-regulated by A beta treatment in a time and dose-dependent manner. Moreover, using overexpression and knock-down strategies, we found that overexpression of STC1 decreased transmigration of monocytes induced by A beta and prevented A beta-induced apoptosis of HBMECs. in addition, we explored the possible mechanisms underlying the effects of STC1, showing that overexpression of STC1 attenuated the effect of A beta on up-regulating early growth response-1 (Egr-1), macrophage inflammatory Protein-1 beta (MIP-1 beta), or cleaved caspase-8. Our data thus indicate a key role of STC1 in the response of HBMECs to A beta exposure. (C) 2008 Elsevier Inc. All rights reserved.