{"title":"用于治疗高甘油三酯血症的 ANGPTL3 和 ApoC-III 抑制剂的背景:马到成功?","authors":"Dick C Chan, Gerald F Watts","doi":"10.1097/MOL.0000000000000920","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Hypertriglyceridemia (HTG) is an independent and casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with HTG. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III) are key regulators of triglyceride-rich lipoprotein (TRL) metabolism. We review recent clinical trials targeting ANGPTL3 and apoC-III with monoclonal antibody and nucleic acid therapies, including antisense oligonucleotides and small interfering RNA.</p><p><strong>Recent findings: </strong>ANGPTL3 and apoC-III inhibitors are effective in lowering plasma triglycerides and TRLs, with possibly greater efficacy with the inhibition of apoC-III. By contrast to ANGPTL3 inhibition that has the advantage of greater lowering of plasma low-density lipoprotein (LDL)-cholesterol and apoB levels, apoC-III inhibition only has a modest or no effect in lowering plasma LDL-cholesterol and apoB concentrations. Therapeutic inhibition of ANGPTL3 and apoC-III can correct HTG possibly by reducing production and increasing catabolism of TRL particles, but this remains to be formally investigated in patients with HTG.</p><p><strong>Summary: </strong>Novel agents targeting ANGPTL3 and apoC-III can correct HTG and potentially lower risk of ASCVD in patients with HTG. The long-term safety and cost-effectiveness of these agents await confirmation in ongoing and future studies.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ANGPTL3 and ApoC-III inhibitors for treating hypertriglyceridemia in context: horses for courses?\",\"authors\":\"Dick C Chan, Gerald F Watts\",\"doi\":\"10.1097/MOL.0000000000000920\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>Hypertriglyceridemia (HTG) is an independent and casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with HTG. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III) are key regulators of triglyceride-rich lipoprotein (TRL) metabolism. We review recent clinical trials targeting ANGPTL3 and apoC-III with monoclonal antibody and nucleic acid therapies, including antisense oligonucleotides and small interfering RNA.</p><p><strong>Recent findings: </strong>ANGPTL3 and apoC-III inhibitors are effective in lowering plasma triglycerides and TRLs, with possibly greater efficacy with the inhibition of apoC-III. By contrast to ANGPTL3 inhibition that has the advantage of greater lowering of plasma low-density lipoprotein (LDL)-cholesterol and apoB levels, apoC-III inhibition only has a modest or no effect in lowering plasma LDL-cholesterol and apoB concentrations. Therapeutic inhibition of ANGPTL3 and apoC-III can correct HTG possibly by reducing production and increasing catabolism of TRL particles, but this remains to be formally investigated in patients with HTG.</p><p><strong>Summary: </strong>Novel agents targeting ANGPTL3 and apoC-III can correct HTG and potentially lower risk of ASCVD in patients with HTG. The long-term safety and cost-effectiveness of these agents await confirmation in ongoing and future studies.</p>\",\"PeriodicalId\":11109,\"journal\":{\"name\":\"Current opinion in lipidology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current opinion in lipidology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/MOL.0000000000000920\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in lipidology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MOL.0000000000000920","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
综述目的:高甘油三酯血症(HTG)是动脉粥样硬化性心血管疾病(ASCVD)的一个独立且偶然的危险因素。高甘油三酯血症患者需要更有效的治疗方法。血管生成素样蛋白 3(ANGPTL3)和载脂蛋白 C-III(apoC-III)是富含甘油三酯的脂蛋白(TRL)代谢的关键调节因子。我们回顾了近期针对ANGPTL3和载脂蛋白C-III的单克隆抗体和核酸疗法(包括反义寡核苷酸和小干扰RNA)的临床试验:ANGPTL3和载脂蛋白C-III抑制剂可有效降低血浆甘油三酯和TRL,其中抑制载脂蛋白C-III的效果可能更好。抑制 ANGPTL3 的优势在于能更大程度地降低血浆低密度脂蛋白(LDL)胆固醇和载脂蛋白 B 水平,相比之下,抑制载脂蛋白 C-III 对降低血浆低密度脂蛋白胆固醇和载脂蛋白 B 浓度的作用不大,甚至没有作用。摘要:靶向 ANGPTL3 和 apoC-III 的新型药物可纠正 HTG,并有可能降低 HTG 患者的 ASCVD 风险。这些药物的长期安全性和成本效益有待当前和未来研究的证实。
ANGPTL3 and ApoC-III inhibitors for treating hypertriglyceridemia in context: horses for courses?
Purpose of review: Hypertriglyceridemia (HTG) is an independent and casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with HTG. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III) are key regulators of triglyceride-rich lipoprotein (TRL) metabolism. We review recent clinical trials targeting ANGPTL3 and apoC-III with monoclonal antibody and nucleic acid therapies, including antisense oligonucleotides and small interfering RNA.
Recent findings: ANGPTL3 and apoC-III inhibitors are effective in lowering plasma triglycerides and TRLs, with possibly greater efficacy with the inhibition of apoC-III. By contrast to ANGPTL3 inhibition that has the advantage of greater lowering of plasma low-density lipoprotein (LDL)-cholesterol and apoB levels, apoC-III inhibition only has a modest or no effect in lowering plasma LDL-cholesterol and apoB concentrations. Therapeutic inhibition of ANGPTL3 and apoC-III can correct HTG possibly by reducing production and increasing catabolism of TRL particles, but this remains to be formally investigated in patients with HTG.
Summary: Novel agents targeting ANGPTL3 and apoC-III can correct HTG and potentially lower risk of ASCVD in patients with HTG. The long-term safety and cost-effectiveness of these agents await confirmation in ongoing and future studies.
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.