Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Curr Opin Lipidol. 2020 Jun;31(3):147-153. doi: 10.1097/MOL.0000000000000680.
Apolipoprotein C-II (apoC-II) is a critical cofactor for the activation of lipoprotein lipase (LPL), a plasma enzyme that hydrolyzes triglycerides (TG) on TG-rich lipoproteins (TRL). Although apoC-II was first discovered nearly 50 years ago, there is renewed interest in it because of the recent efforts to develop new drugs for the treatment of hypertriglyceridemia (HTG). The main topic of this review will be the development of apoC-II mimetic peptides as a possible new therapy for cardiovascular disease.
We first describe the biochemistry of apoC-II and its role in TRL metabolism. We then review the clinical findings of HTG, particularly those related to apoC-II deficiency, and how TG metabolism relates to the development of atherosclerosis. We next summarize the current efforts to develop new drugs for HTG. Finally, we describe recent efforts to make small synthetic apoC-II mimetic peptides for activation of LPL and how these peptides unexpectedly have other mechanisms of action mostly related to the antagonism of the TG-raising effects of apoC-III.
The role of apoC-II in TG metabolism is reviewed, as well as recent efforts to develop apoC-II mimetic peptides into a novel therapy for HTG.
载脂蛋白 C-II（apoC-II）是脂蛋白脂肪酶（LPL）激活的关键辅助因子，LPL 是一种血浆酶，可水解富含甘油三酯（TG）的脂蛋白（TRL）上的 TG。尽管 apoC-II 早在近 50 年前就被首次发现，但由于最近在开发治疗高甘油三酯血症（HTG）的新药方面所做的努力，人们对其又产生了新的兴趣。这篇综述的主要主题将是开发 apoC-II 模拟肽作为治疗心血管疾病的一种新的可能疗法。
我们首先描述了 apoC-II 的生物化学及其在 TRL 代谢中的作用。然后，我们回顾了 HTG 的临床发现，特别是与 apoC-II 缺乏相关的发现，以及 TG 代谢与动脉粥样硬化发展的关系。接下来，我们总结了目前为治疗 HTG 而开发新药的努力。最后，我们描述了最近开发用于激活 LPL 的小合成 apoC-II 模拟肽的努力，以及这些肽出人意料地具有其他作用机制，主要与 apoC-III 的 TG 升高作用拮抗有关。
本文综述了 apoC-II 在 TG 代谢中的作用，以及最近将 apoC-II 模拟肽开发为 HTG 新疗法的努力。
