Abstract 446: Therapeutic Silencing of MicroRna-33 In Mice Inhibits the Progression of Atherosclerosis in Ldlr-/- Mice
Objective-To study the efficacy of anti-miRNA-33 therapy on the progression of atherosclerosis.
Methods and Results-LDLr-/- mice were injected subcutaneously with PBS, control or miR-33 antisense oligonucleotides (ASO) weekly and fed a Western diet for 12 weeks. As expected, hepatic levels of miR-33 were significantly decreased in anti-miR-33 treated mice. Accordingly, the expression of miR-33 target genes was increased in the liver and aorta. Interestingly, plasma HDL cholesterol (HDL-C) was significantly increased in anti-miR-33 treated mice but only when they were fed a chow diet. Analysis of atherosclerosis revealed a significant reduction of plaque size and macrophage content in mice receiving miR-33 ASO. In contrast, no differences in collagen content and necrotic areas were observed between the three groups.
Conclusions-Long-term anti-miR-33 therapy significantly reduces the progression of atherosclerosis. The miR-33 ASO anti-atherogenic effect is independent of plasma HDL-C.
- © 2013 by American Heart Association, Inc.