Angiopoietin-like 3: An important protein in regulating lipoprotein levels

IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Kendall H. Burks (BS, MD-PhD Candidate) , Debapriya Basu (PhD, Research Assistant Professor) , Ira J. Goldberg (MD, Professor of Medicine) , Nathan O. Stitziel (MD, PhD, Associate Professor of Medicine)
{"title":"Angiopoietin-like 3: An important protein in regulating lipoprotein levels","authors":"Kendall H. Burks (BS, MD-PhD Candidate) ,&nbsp;Debapriya Basu (PhD, Research Assistant Professor) ,&nbsp;Ira J. Goldberg (MD, Professor of Medicine) ,&nbsp;Nathan O. Stitziel (MD, PhD, Associate Professor of Medicine)","doi":"10.1016/j.beem.2022.101688","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span>ANGPTL3 has emerged as a therapeutic target whose inhibition results in profound reductions of </span>plasma lipids<span>, including atherogenic triglyceride-rich lipoproteins and low-density lipoprotein cholesterol. The identification of ANGPTL3 deficiency as a cause of familial combined hypolipidemia in humans hastened the development of anti-ANGPTL3 therapeutic agents, including </span></span>evinacumab<span><span> (a monoclonal antibody inhibiting circulating ANGPTL3), vupanorsen (an </span>antisense oligonucleotide [ASO] targeting hepatic </span></span><em>ANGPTL3</em><span><span><span><span> mRNA for degradation), and others. Advances have also been made in ANGPTL3 vaccination and gene editing strategies, with the former still in preclinical phases and the latter in preparation for Phase 1 trials. Here, we review the discovery of ANGPTL3 as an important regulator of </span>lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti-ANGPTL3 agents. The clinical success of </span>therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory </span>hypertriglyceridemia<span> and hypercholesterolemia.</span></span></p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"37 3","pages":"Article 101688"},"PeriodicalIF":6.1000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922336/pdf/","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Best practice & research. Clinical endocrinology & metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521690X22000756","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 3

Abstract

ANGPTL3 has emerged as a therapeutic target whose inhibition results in profound reductions of plasma lipids, including atherogenic triglyceride-rich lipoproteins and low-density lipoprotein cholesterol. The identification of ANGPTL3 deficiency as a cause of familial combined hypolipidemia in humans hastened the development of anti-ANGPTL3 therapeutic agents, including evinacumab (a monoclonal antibody inhibiting circulating ANGPTL3), vupanorsen (an antisense oligonucleotide [ASO] targeting hepatic ANGPTL3 mRNA for degradation), and others. Advances have also been made in ANGPTL3 vaccination and gene editing strategies, with the former still in preclinical phases and the latter in preparation for Phase 1 trials. Here, we review the discovery of ANGPTL3 as an important regulator of lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti-ANGPTL3 agents. The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia.

血管生成素样3:调节脂蛋白水平的重要蛋白
ANGPTL3已成为一种治疗靶点,其抑制作用可显著降低血脂,包括致动脉粥样硬化的富含甘油三酯的脂蛋白和低密度脂蛋白胆固醇。将ANGPTL3缺乏确定为人类家族性联合低脂血症的原因,加速了抗ANGPTL3治疗剂的开发,包括evinacumab(一种抑制循环ANGPTL3的单克隆抗体)、vupanorsen(一种靶向肝脏ANGPTL3 mRNA降解的反义寡核苷酸[ASO])等。ANGPTL3疫苗接种和基因编辑策略也取得了进展,前者仍处于临床前阶段,后者正在为1期试验做准备。在此,我们综述了ANGPTL3作为脂蛋白代谢的重要调节因子的发现、蛋白质的分子特征、调节血脂的机制以及抗ANGPTL3药物的临床开发。抑制ANGPTL3疗法的临床成功突出了该靶点作为治疗难治性高甘油三酯血症和高胆固醇血症的新方法的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
11.90
自引率
0.00%
发文量
77
审稿时长
6-12 weeks
期刊介绍: Best Practice & Research Clinical Endocrinology & Metabolism is a serial publication that integrates the latest original research findings into evidence-based review articles. These articles aim to address key clinical issues related to diagnosis, treatment, and patient management. Each issue adopts a problem-oriented approach, focusing on key questions and clearly outlining what is known while identifying areas for future research. Practical management strategies are described to facilitate application to individual patients. The series targets physicians in practice or training.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信