Analysis of antiapoptotic genes induced in vascular endothelial cells by monocyte adhesion.

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Apoptosis of vascular endothelial cells (EC) and monocyte-EC interaction play a critical role in the development and progression of atherosclerosis. We have found that adhesion of monocyte to EC inhibits BC apoptosis. However, the mechanism by which BC apoptosis is regulated remains to be elucidated. In the present study, we analyzed antiapoptotic genes induced in BC by monocyte adhesion using THP-1, a human monocytic cell line and human umbilical vein endothelial cells (HUVEC). Apoptosis of HUVEC was induced by serum starvation arid examined by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) labeling and caspase-3 activity assay. Apoptosis of. HUVEC was significantly inhibited by THP-1 adhesion. mRNAs were isolated from HUVEC cultured with or without THP-1, and genes induced in HUVEC by THP-1 adhesion were analyzed using a DNA microarray (IntelliGene HS Human Expression CHIP, TAKARA BIO). Adhesion of THP-1 to HUVEC induced expression of many kinds of genes in HUVEC including osteopontin, IL-1, selectin B, PPARgamma, and MCP-1 as well as apoptosis-relaled genes such as bcl-2, caspace-8 and BIK. Among these genes expressed, osteopontin was most prominently upregulated by THP-1 adhesion (558-fold increase). Because osteopontin has been reported to play a role in survival pathways related. to cell adhesion, our data provide a novel insight into the genetic mechanism of inhibition of EC apoptosis induced by monocyte adhesion.