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脂蛋白(a)与动脉粥样硬化性心血管疾病：我们处于何种立场？

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?

机构信息

Fourth Department of Internal Medicine, Medical School, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Second Department of Internal Medicine, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.

出版信息

Int J Mol Sci. 2024 Mar 21;25(6):3537. doi: 10.3390/ijms25063537.

DOI:10.3390/ijms25063537
PMID:38542510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10971284/
Abstract

Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70-90% genetically determined through the codominant expression of the gene. Therefore, Lp(a) levels are almost stable during an individual's lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.

摘要

脂蛋白(a) [Lp(a)] 由一种低密度脂蛋白样分子和载脂蛋白(a) [apo(a)] 颗粒组成。Lp(a) 被认为是动脉粥样硬化性心血管疾病 (ASCVD) 的独立危险因素。Lp(a) 的血浆水平被认为通过基因的共显性表达 70-90%由遗传决定。因此，Lp(a) 水平在个体的一生中几乎是稳定的。这种终生的稳定性，再加上以标准化方式测量 Lp(a) 水平的困难，可能是针对 Lp(a) 的可用药物稀缺的原因。在这篇综述中，我们总结了有关 Lp(a) 的结构、代谢和影响循环水平的因素的最新数据，以及 Lp(a) 的实验室测定测量、它在 ASCVD 和血栓形成发病机制中的作用，以及针对 Lp(a) 的各种治疗药物的潜在用途。特别是，我们讨论了目前正在开发的针对 Lp(a) 的新型药物，如反义寡核苷酸 (ASO) 和小干扰 RNA (siRNA)。然后进一步分析了 Lp(a) 形成的口服抑制剂 muvalaplin 的有前途的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/5337d75bb6d3/ijms-25-03537-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/f8f497a11623/ijms-25-03537-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/d288a68360c6/ijms-25-03537-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/75cdccb305c5/ijms-25-03537-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/5337d75bb6d3/ijms-25-03537-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/f8f497a11623/ijms-25-03537-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/d288a68360c6/ijms-25-03537-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/75cdccb305c5/ijms-25-03537-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ced/10971284/5337d75bb6d3/ijms-25-03537-g004.jpg

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Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?

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[3]
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[4]
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[5]
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[6]
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[7]
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本文引用的文献

[1]
ApoB100 and Atherosclerosis: What's New in the 21st Century?

Metabolites. 2024-2-12

[2]
Impact of elevated lipoprotein(a) on coronary artery disease phenotype and severity.

Eur J Prev Cardiol. 2024-5-11

[3]
Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense?

J Clin Med. 2024-1-28

[4]
Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a).

Sci Rep. 2024-2-2

[5]
Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension.

Int J Mol Sci. 2023-12-26

[6]
Potential of muvalaplin as a lipoprotein(a) inhibitor.

Expert Opin Investig Drugs. 2024-1

[7]
Burden of elevated lipoprotein(a) among patients with atherosclerotic cardiovascular disease: Evidence from a systematic literature review and feasibility assessment of meta-analysis.

PLoS One. 2023

[8]
Traditional and novel non-statin lipid-lowering drugs.

Indian Heart J. 2024-3

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Curr Atheroscler Rep. 2023-12

[10]
Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial.

JAMA. 2023-12-5

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