作为治疗腹主动脉瘤药物靶点的 Proprotein convertase subtilisin/kexin type 9。

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-07-22 DOI:10.1097/MOL.0000000000000945
Jonathan Golledge, Hong S Lu, Sonia Shah
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引用次数: 0

摘要

审查目的:目前尚无限制腹主动脉瘤(AAA)生长的药物疗法。本综述总结了一些证据,这些证据表明,抑制 9 型枯草蛋白/kexin 丙蛋白转换酶(PCSK9)可能是限制 AAA 生长的药物靶点:孟德尔随机化研究表明,低密度脂蛋白和非高密度脂蛋白胆固醇的升高与 AAA 的形成有因果关系。据报道,与器官捐献者的主动脉样本相比,PCSK9在人类AAA样本中上调。PCSK9 功能增益病毒载体可促进注入血管紧张素 II 的 C57BL/6 小鼠主动脉扩张。据报道,在主动脉灌注弹性蛋白酶模型中改变 PCSK9 表达的效果并不一致。编码 PCSK9 的基因突变会增加血清胆固醇,与人类 AAA 风险增加有关。AAA 患者发生心血管死亡、心肌梗死和中风的风险也很高。摘要:过去的研究表明,抑制 PCSK9 的药物有可能成为治疗 AAA 的新型疗法,既能限制动脉瘤的生长,又能降低心血管事件的风险。我们需要一项大型多国随机对照试验来检验 PCSK9 抑制剂是否能限制 AAA 的生长和心血管事件的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proprotein convertase subtilisin/kexin type 9 as a drug target for abdominal aortic aneurysm.

Purpose of review: There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth. This review summarizes evidence suggesting that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) may be a drug target to limit AAA growth.

Recent findings: Mendelian randomization studies suggest that raised LDL and non-HDL-cholesterol are causal in AAA formation. PCSK9 was reported to be upregulated in human AAA samples compared to aortic samples from organ donors. PCSK9 gain of function viral vectors promoted aortic expansion in C57BL/6 mice infused with angiotensin II. The effect of altering PCSK9 expression in the aortic perfusion elastase model was reported to be inconsistent. Mutations in the gene encoding PCSK9, which increase serum cholesterol, were associated with increased risk of human AAA. Patients with AAA also have a high risk of cardiovascular death, myocardial infarction and stroke. Recent research suggests that PCSK9 inhibition would substantially reduce the risk of these events.

Summary: Past research suggests that drugs that inhibit PCSK9 have potential as a novel therapy for AAA to both limit aneurysm growth and reduce risk of cardiovascular events. A large multinational randomized controlled trial is needed to test if PCSK9 inhibition limits AAA growth and cardiovascular events.

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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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