NEJM:Angptl3 反义寡核苷酸与血脂异常

2017-05-28 zhangfan MedSci原创

在小鼠模型和患者中,针对Angptl3 基因的反义寡核苷酸可显著减少导致动脉粥样化的脂蛋白水平

近日研究人员通过流行病学和全基因组关联研究阐明了ANGPTL3功能丧失突变,血管生成素样3与血浆脂蛋白水平降低的关系。同期还有一篇文章也发现该基因与冠心病有关:NEJM:ANGPTL3与冠心病风险

首先,研究人员在小鼠模型中通过反义寡核苷酸技术研究了ANGPTL3对血脂水平,甘油三酯清除,肝脏甘油三酯含量、胰岛素敏感性和动脉粥样硬化进展的影响。随后研究招募了44名高甘油三酯志愿者,随机接受安慰剂或ANGPTL3 mRNA反义寡核苷酸(单剂量20,40或80 mg;多剂量10,20,40或60mg 每周持续6周)。主要终点是安全性,副作用,药代动力学和药效学,血脂和脂蛋白水平的变化。

研究发现,在小鼠模型中,反义寡核苷酸存在剂量依赖的肝组织Angptl3mRNA表达减少,Angptl3蛋白表达减少,甘油三酯减少,低密度脂蛋白(LDL)胆固醇减少,以及肝脏甘油三酯含量的降低与动脉粥样硬化的进展减慢和胰岛素敏感性增加。在人体试验中,服药6周后,相比于安慰剂,多剂量组患者ANGPTL3蛋白水平降低(较基线下降,同下44.6-84.5%),甘油三酯降低(33.2-63.1%),LDL 胆固醇下降(1.3 -32.9%), 极LDL胆固醇下降(27.9 -60.0%), 非HDL胆固醇下降(10.0 -36.6%), 载脂蛋白B下降 (3.4 - 25.7%)以及载脂蛋白C-III 下降(18.9 -58.8%)。三名接受反义寡核苷酸和三接受安慰剂的参与者报告头晕或头痛,无严重不良事件。

在小鼠模型和患者中,针对Angptl3 基因的反义寡核苷酸可显著减少导致动脉粥样化的脂蛋白水平。

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    2018-05-04 xsm918
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    2017-05-29 执着追梦

    学习,感谢分享

    0

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    2017-05-29 cqykthl

    反义寡核苷酸可显著减少导致动脉粥样化的脂蛋白水平。

    0

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    2017-05-29 184****9840

    学习了谢谢分享。

    0

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    2017-05-28 忠诚向上

    好好努力学习

    0

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    2017-05-28 有备才能无患

    小鼠模型和患者中,针对Angptl3基因的反义寡核苷酸可显著减少导致动脉粥样化的脂蛋白水平。

    0

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