Effects of Antiatherosclerosis in Carotid Artery by RNAi-Mediated Silencing of MCP-1 Expression
Background Our objective was to identify the effects of MCP-1 siRNA in vivo transfection in an atherosclerosis model on local expression of MCP-1 and pathogenesis of atherosclerosis. Methods Carotid atherosclerosis was induced in 28 New Zealand white rabbits. Rabbits were divided into three groups r...
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Veröffentlicht in: | Annals of vascular surgery 2009-09, Vol.23 (5), p.652-662 |
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Zusammenfassung: | Background Our objective was to identify the effects of MCP-1 siRNA in vivo transfection in an atherosclerosis model on local expression of MCP-1 and pathogenesis of atherosclerosis. Methods Carotid atherosclerosis was induced in 28 New Zealand white rabbits. Rabbits were divided into three groups randomly: RNAi group, model group, and blank plasmid group. siRNA-expressing vector was transfected to blood vessels by liposomes. The carotid arteries were processed for morphological evaluation. Local expression of MCP-1 was detected by immunohistochemistry, RT-PCR, and Western blot. Results On hematoxylin and eosin–stained sections, partial endothelial cells detached while intimae were less thickened in the RNAi group compared to the model and blank plasmid groups; the I:M ratio was significantly reduced to 1.46 in the RNAi group compared to the model and blank plasmid groups (5.55 and 5.27, respectively). The results of immunohistochemistry showed that MCP-1 expression was less colorized and less positive in the RNAi group. RT-PCR and Western blot showed reduced expression in the RNAi group than in the model and blank plasmid groups. There were highly positive correlations between semiquantitative RT-PCR and the I:M ratio ( r = 0.968). Conclusion Expression of MCP-1 was successfully inhibited by transfecting MCP-1 siRNA expression plasmid to the carotid artery, and the progression of atherosclerosis was restricted by RNAi-mediated silencing of MCP-1 expression. |
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ISSN: | 0890-5096 1615-5947 |
DOI: | 10.1016/j.avsg.2009.01.002 |