AntimiR-33 Therapy Does Not Alter the Progression of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Objective—To determine the efficacy of long-term antimiR-33 therapy on the progression of atherosclerosis in high-fat, high-cholesterol–fed Ldlr–/– mice.
Methods and Results—Ldlr–/– mice received saline, or control or antimiR-33 oligonucleotides once a week for 14 weeks. The treatment was effective, as measured by reduced levels of hepatic miR-33 and increased hepatic expression of miR-33 targets. Analysis of plasma samples revealed an initial elevation in high-density lipoprotein cholesterol after 2 weeks of treatment that was not sustained by the end of the experiment. Additionally, we found a significant increase in circulating triglycerides in antimiR-33–treated mice, compared with controls. Finally, examination of atheromata revealed no significant changes in the size or composition of lesions between the 3 groups.
Conclusion—Prolonged silencing of miR-33 fails to maintain elevated plasma high-density lipoprotein cholesterol and does not prevent the progression of atherosclerosis in Ldlr–/– mice.
- Received October 11, 2012.
- Accepted December 12, 2012.
- © 2013 American Heart Association, Inc.