Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice.
Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice.
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DOI：
10.1161/atvbaha.112.300639
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Baldán Á
中科院分区：
文献类型：
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作者：
Marquart TJ;Wu J;Lusis AJ;Baldán Á
旨在确定长期抗 miR-33 治疗对高脂肪、高胆固醇喂养的 Ldlr−/− 小鼠动脉粥样硬化进展的功效。 Ldlr−/− 小鼠每周接受一次盐水、对照或抗 miR-33 寡核苷酸，持续 14 周。通过肝脏 miR-33 水平降低和 miR-33 靶标肝脏表达增加来衡量，治疗是有效的。血浆样本分析显示，治疗两周后，HDL-胆固醇最初升高，但到实验结束时并未持续升高。此外，我们发现与对照组相比，抗 miR-33 治疗小鼠的循环甘油三酯显着增加。最后，动脉粥样硬化检查显示三组之间病变的大小或成分没有显着变化。长期沉默 miR-33 无法维持 Ldlr−/− 小鼠血浆 HDL 胆固醇升高，也不能阻止动脉粥样硬化的进展。
To determine the efficacy of long-term anti-miR-33 therapy on the progression of atherosclerosis in high fat, high cholesterol-fed Ldlr−/− mice. 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 HDL-cholesterol after two 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 to controls. Finally, examination of atheromata revealed no significant changes in the size or composition of lesions between the three groups. Prolonged silencing of miR-33 fails to maintain elevated plasma HDL-cholesterol and does not prevent the progression of atherosclerosis in Ldlr−/− mice.