Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice
TJ Marquart, J Wu, AJ Lusis… - … , thrombosis, and vascular …, 2013 - Am Heart Assoc
TJ Marquart, J Wu, AJ Lusis, Á Baldán
Arteriosclerosis, thrombosis, and vascular biology, 2013•Am Heart AssocObjective—To determine the efficacy of long-term anti-miR-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 anti-miR-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 …
atherosclerosis in high-fat, high-cholesterol–fed Ldlr–/–mice. Methods and Results—Ldlr–/–
mice received saline, or control or anti-miR-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 …
Objective
To determine the efficacy of long-term anti-miR-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 anti-miR-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 anti-miR-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.
Am Heart Assoc