Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells

Article

关键词: LOW-DENSITY-LIPOPROTEIN;    SMOOTH-MUSCLE CELLS;    MIGRATION IN-VITRO;    TRANSENDOTHELIAL MIGRATION;    GENE-EXPRESSION;    CHEMOTACTIC PROTEIN-1;    RECEPTOR;    OLIGONUCLEOTIDES;    ATHEROGENESIS;    ACTIVATION;   

DOI  :  10.1161/01.CIR.101.25.2889

来源: SCIE

【 摘 要 】

Background-We have recently demonstrated a lectin-like receptor for oxidized (ox)-LDL (LOX-1) in human coronary artery endothelial cells (HCAECs). This receptor is upregulated by ox-LDL. The present study examined the significance of LOX-1 in monocyte adhesion to HCAECs and endothelial injury in response to ox-LDL. Methods and Results-HCAECs were incubated in the presence of antisense oligodeoxynucleotides to the 5'-coding sequence of the human LOX-1 gene (0.5 mu m/L) Basal LOX-1 mRNA and protein were suppressed by antisense LOX-1. Ox-LDL-mediated upregulation of LOX-1 was also suppressed by antisense LOX-1. Incubation of HCAECs with ox-LDL (40 mu g/mL) for 24 hours markedly increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression as well as monocyte adhesion to HCAECs (P<0.01). After 48 hours of preincubation of HCAECs with antisense LOX-1, ox-LDL-mediated upregulation of MCP-1 and monocyte adhesion to HCAECs both were suppressed (P<0.01), whereas sense LOX-1 had no effect. Whereas antisense or sense LOX-1 alone (both 0.5 nmol/L) did not injure the cells, antisense LOX-1, but not sense LOX-1, reduced ox-LDL-mediated HCAEC injury, determined as LDH release (P<0.01). Activation of mitogen-activated protein kinase (MAPK) may play a critical role in signal transduction in ox-LDL-mediated alteration in MCP-1 expression, since antisense LOX-1, but not the sense LOX-1, completely inhibited the ox-LDL-induced MAPK activation. Conclusions-These observations with the first use of a specific antisense to human LOX-1 mRNA suggest that LOX-1 is a key factor in ox-LDL-mediated monocyte adhesion to HCAECs.

【 授权许可】

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