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小干扰RNA对脂蛋白(a)的影响：一项系统评价

Small interfering RNA effect on lipoprotein(a): a systematic review.

作者信息

Almaadawy Omar, Hesn Mohamed Mar'ey, Elsalamony Yomna Ayman, Abobakr Omar Ayman, Elshimy Abdelrahman Hossam, Abulkhair Khaled Alsayed, Negm Mahmoud Mohamed, Shaban Ahmed Yasser, Bene-Alhasan Yakubu, Annie Frank, Belcher Adam, Elashery Ahmed Ramy

机构信息

Internal Medicine Department, MedStar Health, 201 E. University Pkwy, Baltimore, MD, 21218, USA.

Faculty of Medicine, Al Azhar University, New Damietta, Egypt.

出版信息

Egypt Heart J. 2025 May 8;77(1):44. doi: 10.1186/s43044-025-00635-1.

DOI:10.1186/s43044-025-00635-1
PMID:40338464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12062474/
Abstract

BACKGROUND: This systematic review investigates the effect of small interfering RNA (siRNA) therapies on lipoprotein(a) [Lp(a)] levels. The purpose is to evaluate the outcomes of recent randomized controlled trials (RCTs) involving siRNA treatments aimed at lowering Lp(a) levels, a known cardiovascular risk factor. METHODS: A comprehensive search across multiple databases was conducted, identifying 20 published and ongoing RCTs that examined the effects of siRNA therapies such as inclisiran, olpasiran, and SLN360 on Lp(a) levels. The included studies were analyzed to assess Lp(a) reductions and other lipid-related outcomes. RESULTS: The RCTs demonstrated significant reductions in Lp(a) levels following siRNA therapy. Additional reductions were noted in LDL-c and apolipoprotein B levels. Side effects were typically mild, including injection site reactions. CONCLUSIONS: siRNA therapies show promise in effectively lowering Lp(a) levels, with minimal adverse effects. However, further research is required to establish their long-term safety and efficacy.

摘要

背景：本系统评价研究了小干扰RNA（siRNA）疗法对脂蛋白(a) [Lp(a)]水平的影响。目的是评估近期涉及旨在降低Lp(a)水平（一种已知的心血管危险因素）的siRNA治疗的随机对照试验（RCT）结果。 方法：对多个数据库进行了全面检索，确定了20项已发表和正在进行的RCT，这些试验研究了inclisiran、olpasiran和SLN360等siRNA疗法对Lp(a)水平的影响。对纳入的研究进行分析，以评估Lp(a)的降低情况和其他与脂质相关的结果。 结果：RCT表明，siRNA治疗后Lp(a)水平显著降低。低密度脂蛋白胆固醇（LDL-c）和载脂蛋白B水平也有额外降低。副作用通常较轻，包括注射部位反应。 结论：siRNA疗法有望有效降低Lp(a)水平，且副作用最小。然而，需要进一步研究以确定其长期安全性和有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/fa87e0aa17c0/43044_2025_635_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/394293202e18/43044_2025_635_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/0a9f1c83e47a/43044_2025_635_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/057e9f6b12cc/43044_2025_635_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/fa87e0aa17c0/43044_2025_635_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/394293202e18/43044_2025_635_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/0a9f1c83e47a/43044_2025_635_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/057e9f6b12cc/43044_2025_635_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08f/12062474/fa87e0aa17c0/43044_2025_635_Fig4_HTML.jpg

相似文献

[1]
Small interfering RNA effect on lipoprotein(a): a systematic review.

Egypt Heart J. 2025-5-8

[2]
Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta-analysis.

Diabetes Obes Metab. 2025-6

[3]
The Promise of PCSK9 and Lipoprotein(a) as Targets for Gene Silencing Therapies.

Clin Ther. 2023-11

[4]
Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels.

JAMA. 2022-5-3

[5]
Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies.

Pharmacotherapy. 2023-10

[6]
Recent lipoprotein(a) trials.

Curr Opin Lipidol. 2022-12-1

[7]
The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results.

J Am Coll Cardiol. 2024-8-27

[8]
Efficacy of Traditional Anti-lipidemic Drugs in Lowering Lipoprotein(a) Levels: A Systematic Review.

Cureus. 2024-9-20

[9]
Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

PLoS One. 2023

[10]
Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?

Cardiol Ther. 2024-3

本文引用的文献

[1]
Recent progress in gene therapy for familial hypercholesterolemia treatment.

iScience. 2024-8-10

[2]
Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial.

JAMA. 2023-12-5

[3]
Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

Int J Environ Res Public Health. 2023-9-6

[4]
LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics.

Annu Rev Pharmacol Toxicol. 2024-1-23

[5]
Extreme lipoprotein(a) in clinical practice: A cross sectional study.

Int J Cardiol Cardiovasc Risk Prev. 2023-1-13

[6]
Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials.

Cardiovasc Drugs Ther. 2024-6

[7]
Comparison of Current International Guidelines for the Management of Dyslipidemia.

J Clin Med. 2022-12-6

[8]
Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.

N Engl J Med. 2022-11-17

[9]
Effect of inclisiran on lipids in primary prevention: the ORION-11 trial.

Eur Heart J. 2022-12-21

[10]
Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies.

J Clin Med. 2022-10-13

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