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首页> 外文期刊>Clinical lipidology. >The potential use of monoclonal antibodies and other novel agents as drugs to lower LDL cholesterol
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The potential use of monoclonal antibodies and other novel agents as drugs to lower LDL cholesterol

机译：单克隆抗体和其他新型药物作为降低LDL胆固醇的药物的潜在用途

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LDL cholesterol (LDL-C) is central to the pathogenesis of atherosclerosis and lowering LDL-C is an important component of cardiovascular disease prevention. This article briefly reviews current LDL-C-lowering strategies and then focuses on novel strategies to reduce LDL-C. Lead compounds of the thyromimetic and squalene synthase inhibitor classes were discontinued due to toxicity. Currently, three novel strategies for LDL-C reduction are in clinical development. Hepatic apoB100 production can be reduced with an antisense oligonucleotide (mipomersen), while production of apoB-containing lipoproteins in the gut and liver is reduced by an inhibitor of microsomal triglyceride transfer protein (lomitapide). apoB-containing lipoprotein clearance can also be enhanced by inhibiting PCSK9. Secreted PCSK9 targets LDL receptors for degradation. As PCSK9 levels are upregulated by statin therapy, PCSK9 inhibition may complement statin therapy. Of the multiple strategies to inhibit PCSK9 under development, monoclonal antibodies have progressed furthest in their clinical development.
机译：LDL胆固醇（LDL-C）是动脉粥样硬化发病机制的核心，降低LDL-C是预防心血管疾病的重要组成部分。本文简要回顾了当前降低LDL-C的策略，然后重点介绍了降低LDL-C的新颖策略。由于毒性，已停止使用胸腺嘧啶和角鲨烯合酶抑制剂类别的先导化合物。目前，临床上正在开发三种降低LDL-C的新策略。可以通过反义寡核苷酸（mipomersen）减少肝脏apoB100的产生，而通过微粒体甘油三酸酯转移蛋白（lomitapide）的抑制剂可以减少肠道和肝脏中含apoB的脂蛋白的产生。含apoB的脂蛋白清除率也可以通过抑制PCSK9来提高。分泌的PCSK9靶向LDL受体进行降解。由于他汀类药物治疗可上调PCSK9的水平，因此PCSK9抑制作用可作为他汀类药物治疗的补充。在开发中抑制PCSK9的多种策略中，单克隆抗体在其临床开发中进展最快。

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