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 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.