| The increase of monocyte chemotactic protein 1(MCP-1) expression is one of the performances of endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (LOX-1) is a new specific receptor of ox-LDL. Some studies show that oxidized low density lipoprotein (ox-LDL) can induce the expression of MCP-1 mediated by LOX-1 in HUVECs. The expression of MCP-1 can be inhibited by antisense mRNA of LOX-1. This result indicates that LOX-1 plays an important role in the MCP-1 expression induced by ox-LDL in endothelial cells. LOX-1 does not appear to couple to G protein, and does not possess definite kinase or cyclase domains phosphorylation sites. However, LOX-1 can activate the PKC signaling pathway and the tyrosine kinase pathway. How LOX-1 mediates this signal transduction is still unknown. Various signaling molecules aggregate in caveolae. Caveolin-1(CAV-1) is the signal transduction centre of Caveolae and takes part in several signal pathways. Our previous confocal result shows that LOX-1 and CAV-1 colocalize in CHO cells. It suggests that CAV-1 may take part in the LOX-1 signal pathway induced by ox-LDL in endothelial cells.Our confocal result shows that LOX-1 and CAV-1 colocalize in HUVECs. 3 pairs of cav-1 siRNA were transiently transfected into HUVECs respectively. According to the change of the cav-1 expression in these groups, we screened one pair of effective specific cav-1 siRNA. On the basis of these results, HUVECs were divided into three groups: the control group (normal medium); ox-LDL stimulation group (incubated with 100mg/L ox-LDL for 24h without cav-1 siRNA transfected); cav-1 siRNA group (transfection specific cav-1 siRNA for 24 hours, then incubated with 100mg/L ox-LDL for 24h). The expression of MCP-1 in HUVECs was detected by RT-PCR and ELISA. Compared with the control group, the expression of MCP-1 in the ox-LDL stimulated group has a significant increase (P <0.05). Compared with the ox-LDL stimulated group, the expression of MCP-1 decreased greatly in the cav-1 siRNA group (P <0.05). Our results show that silence of CAV-1 can inhibit the expression of MCP-1 induced by ox-LDL in endothelial cells. It suggests that CAV-1 may play an important role in the signaling pathway of ox-LDL-induced endothelial dysfunction. We will further investigate that the role of CAV-1 in the LOX-1 mediated signal transduction by mutant's construction, FRET and other technologies. |
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