Leveraging drug-target Mendelian randomization for tailored lipoprotein-lipid lowering.

IF 4.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2025-02-20 DOI:10.1097/MOL.0000000000000977
Eloi Gagnon, Benoit J Arsenault
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引用次数: 0

Abstract

Purpose of review: The study of naturally occurring genetic variation in human populations has laid the foundation for proprotein converts subtilisin/kexin type 9 inhibitors, and more recently new classes of lipid-lowering drugs such as lipoprotein(a) inhibitors and lipoprotein lipase pathway activators. These emerging therapies lower plasma lipoprotein-lipid levels that are not adequately managed by traditional low-density lipoprotein (LDL) cholesterol-lowering medications. By targeting different risk factors, these therapies could help manage the important residual cardiovascular risk of LDL cholesterol medications.

Recent findings: We review the latest insights into the pharmacological and genetic modulation of these new therapeutic targets. We highlight that the drugs remarkably recapitulate the lipid effects observed in genetic studies. In addition to lowering lipoprotein-lipid levels, robust genetic evidence support that these drugs may prevent cardiometabolic outcomes.

Summary: Emerging lipid-lowering therapies could launch a new era for preventive medicine in which treatments are optimally tailored to patient's lipoprotein-lipid profiles.

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利用药物靶向孟德尔随机化来降低脂蛋白脂。
综述目的:对人群中自然发生的遗传变异的研究为蛋白转化枯草杆菌素/kexin 9型抑制剂以及最近的新型降脂药物(如脂蛋白(a)抑制剂和脂蛋白脂肪酶途径激活剂)的研究奠定了基础。这些新兴疗法降低了传统低密度脂蛋白(LDL)降胆固醇药物无法充分控制的血浆脂蛋白-脂质水平。通过针对不同的危险因素,这些疗法可以帮助控制低密度脂蛋白胆固醇药物的重要残留心血管风险。最近的发现:我们回顾了这些新的治疗靶点的药理学和遗传调节的最新见解。我们强调,这些药物显著概括了遗传研究中观察到的脂质效应。除了降低脂蛋白-脂质水平外,强有力的遗传证据支持这些药物可能预防心脏代谢结果。总结:新兴的降脂疗法可以开启预防医学的新时代,其中治疗可以根据患者的脂蛋白-脂质谱进行最佳定制。
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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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