ApoC-III as Therapeutic Target: Is it Primetime for Clinical Use?

IF 5.2 2区医学 Q1 PERIPHERAL VASCULAR DISEASE

Current Atherosclerosis Reports Pub Date : 2025-07-18 DOI:10.1007/s11883-025-01315-w

Marta Biolo, Federica Galimberti, Camilla Portinari, Sandra Bertocco, Paola Tosin, Manuela Casula, Lorenzo Previato, Sabina Zambon, Paolo Simioni, Alberto Zambon

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引用次数: 0

Abstract

Purpose of review: Apolipoprotein C-III (ApoC-III) plays a pivotal role in triglyceride (TG) metabolism by inhibiting lipoprotein lipase and hepatic clearance of TG-rich lipoproteins, contributing to hypertriglyceridaemia and elevated cardiovascular risk, as well as a high risk of acute pancreatitis. This review aims to summarize current evidence on ApoC-III inhibition strategies.

Recent findings: Current treatments targeting Apo C-III include two antisense oligonucleotides (ASOs) (volanesorsen and olezarsen), and a small interfering RNA (siRNA) (plozasiran). Volanesorsen, a second-generation ASO, has shown effectiveness in reducing TG and preventing acute pancreatitis, especially in patients with familial chylomicronemia syndrome (FCS). However, its use is limited by the risk of thrombocytopenia, likely related to its chemical structure rather than ApoC-III inhibition itself. Olezarsen, a third-generation ASO with GalNAc conjugation for targeted liver delivery, offers an improved safety profile and strong efficacy in lowering TG and atherogenic lipoproteins levels, making it a promising candidate for a broader clinical use. Plozasiran, a GalNAc-conjugated siRNA, has shown robust and sustained TG reductions with a favorable safety profile, and early data suggest it may also reduce acute pancreatitis risk. ApoC-III inhibition represents an innovative and effective approach in managing hypertriglyceridaemia and its complications. Further outcome-driven trials are essential to define its role in cardiovascular risk reduction.

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ApoC-III作为治疗靶点：是临床应用的最佳时机吗？

载脂蛋白C-III （ApoC-III）通过抑制脂蛋白脂肪酶和肝脏对富含TG的脂蛋白的清除，在甘油三酯（TG）代谢中起关键作用，导致高甘油三酯血症和心血管风险升高，以及急性胰腺炎的高风险。本综述旨在总结ApoC-III抑制策略的现有证据。最新发现：目前针对载脂蛋白C-III的治疗包括两种反义寡核苷酸（volanesorsen和olezarsen）和一种小干扰RNA (siRNA) （plzasiran）。Volanesorsen是第二代ASO，已显示出降低TG和预防急性胰腺炎的有效性，特别是对家族性乳糜小铁血症综合征（FCS）患者。然而，它的使用受到血小板减少风险的限制，这可能与它的化学结构而不是ApoC-III抑制本身有关。Olezarsen是第三代靶向肝脏递送的ASO，具有GalNAc偶联物，具有更好的安全性和降低TG和致动脉粥样硬化脂蛋白水平的强大功效，使其成为广泛临床应用的有希望的候选药物。plzasiran是一种galnac偶联siRNA，已显示出强大且持续的TG降低，具有良好的安全性，早期数据表明它也可能降低急性胰腺炎的风险。ApoC-III抑制是管理高甘油三酯血症及其并发症的一种创新和有效的方法。进一步的结果驱动试验对于确定其在降低心血管风险中的作用至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Atherosclerosis Reports 医学-

CiteScore

9.00

自引率

3.40%

发文量

审稿时长

6-12 weeks

期刊介绍： The aim of this journal is to systematically provide expert views on current basic science and clinical advances in the field of atherosclerosis and highlight the most important developments likely to transform the field of cardiovascular prevention, diagnosis, and treatment. We accomplish this aim by appointing major authorities to serve as Section Editors who select leading experts from around the world to provide definitive reviews on key topics and papers published in the past year. We also provide supplementary reviews and commentaries from well-known figures in the field. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.