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反义载脂蛋白[a]治疗:现状与未来展望。

Antisense lipoprotein[a] therapy: State-of-the-art and future perspectives.

机构信息

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.

出版信息

Eur J Intern Med. 2020 Jun;76:8-13. doi: 10.1016/j.ejim.2020.04.036. Epub 2020 Apr 24.


DOI:10.1016/j.ejim.2020.04.036
PMID:32336611
Abstract

Several lines of evidence now attest that lipoprotein[a] (Lp[a]) is a significant risk factor for many cardiovascular disorders. This enigmatic lipoprotein, composed of a single copy of apolipoprotein B (apoB) and apolipoprotein[a] (apo [a]), expresses peculiar metabolism, virtually independent from lifestyle interventions. Several therapeutic options have hence been proposed for lowering elevated Lp[a] values, with or without concomitant effect on low density lipoprotein (LDL) particles, mostly encompassing statins, ezetimibe, nicotinic acid, lipoprotein apheresis, and anti-PCSK9 monoclonal antibodies. Since all these medical treatments have some technical and clinical drawbacks, a novel strategy is currently being proposed, based on the use of antisense apo[a] and/or apoB inhibitors. Although the role of these agents in hypercholesterolemic patients is now nearby entering clinical practice, the collection of information on Lp[a] is still underway. Preliminary evidence would suggest that apo[a] antisense therapy seems more appropriate in patients with isolated Lp[a] elevations, while apoB antisense therapy is perhaps more advisable in patients with isolated LDL elevations. In patients with concomitant elevations of Lp[a] and LDL, either combining the two apo[a] and apoB antisense therapies (a strategy which has never been tested), or the combination of well-known and relatively inexpensive drugs such as statins with antisense apo[a] inhibitors can be theoretically suggested. The results of an upcoming phase 3 study with antisense apo[a] inhibitors will hopefully provide definitive clues as to whether this approach may become the standard of care in patients with increased Lp[a] concentrations.

摘要

目前有几条证据表明脂蛋白[a](Lp[a])是许多心血管疾病的重要危险因素。这种神秘的脂蛋白由一个载脂蛋白 B(apoB)和载脂蛋白[a](apo[a])组成,其代谢方式独特,几乎与生活方式干预无关。因此,已经提出了几种降低升高的 Lp[a]值的治疗选择,无论是否同时对低密度脂蛋白(LDL)颗粒产生影响,这些选择大多包括他汀类药物、依折麦布、烟酸、脂蛋白吸附和抗 PCSK9 单克隆抗体。由于所有这些治疗方法都存在一些技术和临床上的缺陷,目前正在提出一种新的策略,基于使用反义 apo[a]和/或 apoB 抑制剂。虽然这些药物在高胆固醇血症患者中的作用目前即将进入临床实践,但关于 Lp[a]的信息收集仍在进行中。初步证据表明,apo[a]反义疗法在单纯 Lp[a]升高的患者中似乎更为合适,而 apoB 反义疗法在单纯 LDL 升高的患者中可能更为合适。在 Lp[a]和 LDL 同时升高的患者中,可以考虑联合使用两种 apo[a]和 apoB 反义疗法(这是一种从未经过测试的策略),或者联合使用他汀类等知名且相对便宜的药物与反义 apo[a]抑制剂,理论上可以建议。即将进行的反义 apo[a]抑制剂 3 期研究的结果有望为这种方法是否可能成为升高 Lp[a]浓度患者的标准治疗方法提供明确的线索。

相似文献

[1]
Antisense lipoprotein[a] therapy: State-of-the-art and future perspectives.

Eur J Intern Med. 2020-6

[2]
Lipoprotein (a) and Low-density lipoprotein apolipoprotein B metabolism following apheresis in patients with elevated lipoprotein(a) and coronary artery disease.

Eur J Clin Invest. 2018-12-13

[3]
PCSK9 Inhibition with alirocumab increases the catabolism of lipoprotein(a) particles in statin-treated patients with elevated lipoprotein(a).

Metabolism. 2020-3-30

[4]
New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes.

Clin Ther. 2013-8-8

[5]
Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a).

J Clin Lipidol. 2016

[6]
Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.

Arterioscler Thromb Vasc Biol. 2015-10-29

[7]
Relationship between "LDL-C", estimated true LDL-C, apolipoprotein B-100, and PCSK9 levels following lipoprotein(a) lowering with an antisense oligonucleotide.

J Clin Lipidol. 2018-3-1

[8]
Can Lp(a) Lowering Against Background Statin Therapy Really Reduce Cardiovascular Risk?

Curr Atheroscler Rep. 2019-3-7

[9]
Fractional turnover of apolipoprotein(a) and apolipoprotein B-100 within plasma lipoprotein(a) particles in statin-treated patients with elevated and normal Lp(a) concentration.

Metabolism. 2019-4-14

[10]
Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities.

J Intern Med. 2020-1

引用本文的文献

[1]
Lipoprotein(a) and Lung Function Are Associated in Older Adults: Longitudinal and Cross-Sectional Analyses.

Biomedicines. 2024-7-6

[2]
Lipoprotein (a) as a Biomarker for Cardiovascular Diseases and Potential New Therapies to Mitigate Risk.

Curr Vasc Pharmacol. 2024

[3]
Relationship between lipoprotein(a) levels, cardiovascular outcomes and death in patients with chronic kidney disease: a systematic review of prospective studies.

J Nephrol. 2023-7

[4]
Apolipoproteins in vascular biology and atherosclerotic disease.

Nat Rev Cardiol. 2022-3

[5]
Lipoprotein (a) level as a risk factor for stroke and its subtype: A systematic review and meta-analysis.

Sci Rep. 2021-8-2

[6]
Pyrrolidine Compounds as Potential Lipid-Lowering Therapeutic in Cardiovascular Disease.

ACS Med Chem Lett. 2021-3-16

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