摘要
Background MicroRNAs （miRNANAs） are endogenous, small non-coding RNAs that negatively regulate gene expression in diverse cardiovascular diseases. However, the roles of miRNANAs in atherosclerogenesis needs to be elucidated. In the present study, the effect of miRNA-21 on pro-atherosclerotic genes expression was examined. Methods The pro-atherosclerotic genes including COX2, VCAM1, ICAM1, MCP1 and miRNA-21 were detected in ox-LDL-treated mouse macrophage RAW264.7 cells. ApoE knock-out （ApoE- KO） mice were fed with high-fat diet for 16 weeks, and the abdominal aorta were fixed and used for miRNA- 21 hybridization. Lentivirus-based vectors for enforced expression of miRNA-21 and antisense miRNA-21were prepared. The expression of proatherosclerotic genes was determined in the RAW264.7 cells with lentivirus- mediated up-regulation of miRNA-21. Results COX2, VCAM1, ICAM1 and MCP1 could be up-regulated by ox-LDL treatment, and 50 Ixg/mL ox-LDL could significantly increase the expression of above four genes in ox-LDL EAW264.7 cells, miRNA-21 could also be markedly up-regulated in ox-LDL-induced RAW264.7 cells. The result of miRNANA hybridization showed that miRNA-21 was strongly expressed in atherosclerotic plaques but not in normal aorta. Lentivirus-mediated over-expression of miRNA-21 could significantly enhance expressions of COX2, VCAM1, ICAM1 and MCP1 in RAW264.7 cells, which could be reversed by antisense miRNA-21 mediated by lentivirus vector. Conclusions miRNA-21 could be modulated by ox-LDL in macrophage RAW264.7 cells, and miRNA-21 could enhance COX2, VCAM1, ICAM1 and MCP1 expressions in macrophages.
Background MicroRNAs （miRNANAs） are endogenous, small non-coding RNAs that negatively regulate gene expression in diverse cardiovascular diseases. However, the roles of miRNANAs in atherosclerogenesis needs to be elucidated. In the present study, the effect of miRNA-21 on pro-atherosclerotic genes expression was examined. Methods The pro-atherosclerotic genes including COX2, VCAM1, ICAM1, MCP1 and miRNA-21 were detected in ox-LDL-treated mouse macrophage RAW264.7 cells. ApoE knock-out （ApoE- KO） mice were fed with high-fat diet for 16 weeks, and the abdominal aorta were fixed and used for miRNA- 21 hybridization. Lentivirus-based vectors for enforced expression of miRNA-21 and antisense miRNA-21were prepared. The expression of proatherosclerotic genes was determined in the RAW264.7 cells with lentivirus- mediated up-regulation of miRNA-21. Results COX2, VCAM1, ICAM1 and MCP1 could be up-regulated by ox-LDL treatment, and 50 Ixg/mL ox-LDL could significantly increase the expression of above four genes in ox-LDL EAW264.7 cells, miRNA-21 could also be markedly up-regulated in ox-LDL-induced RAW264.7 cells. The result of miRNANA hybridization showed that miRNA-21 was strongly expressed in atherosclerotic plaques but not in normal aorta. Lentivirus-mediated over-expression of miRNA-21 could significantly enhance expressions of COX2, VCAM1, ICAM1 and MCP1 in RAW264.7 cells, which could be reversed by antisense miRNA-21 mediated by lentivirus vector. Conclusions miRNA-21 could be modulated by ox-LDL in macrophage RAW264.7 cells, and miRNA-21 could enhance COX2, VCAM1, ICAM1 and MCP1 expressions in macrophages.
基金
supported by Grants from the National Natural Science Foundation of China(No.81070102,81270222,81273516,81302779)
the Natural Science Foundation of the Guangdong Province(No.S2011020005911,S2012010009453)
