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靶向脂蛋白(a)的反义疗法的作用。

The Role of Antisense Therapies Targeting Lipoprotein(a).

机构信息

Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York; and.

Shield Health Solutions, Stoughton, MA.

出版信息

J Cardiovasc Pharmacol. 2021 Jul 1;78(1):e5-e11. doi: 10.1097/FJC.0000000000001045.


DOI:10.1097/FJC.0000000000001045
PMID:34232223
Abstract

Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.

摘要

动脉粥样硬化性心血管疾病(ASCVD)仍然是美国可预防死亡的主要原因。众所周知,低密度脂蛋白胆固醇(LDL-C)升高会导致心血管疾病。降低 LDL-C 和 ASCVD 风险的主要治疗方法是他汀类药物治疗。尽管通过降脂治疗达到了理想的 LDL-C 水平,但心血管残余风险仍然存在。脂蛋白(a) [Lp(a)]水平升高已被强调为 ASCVD 的固有独立预测因素,降低 Lp(a)水平可能会显著降低高危患者的残余风险。迄今为止,尚无降低 Lp(a)水平的批准药物。烟酸、前蛋白转化酶枯草溶菌素/激肽释放酶 9 抑制剂和反义寡核苷酸已证明具有适度至强效的 Lp(a)降低作用。反义寡核苷酸及其在降低 Lp(a)中的作用备受关注。APO(a)LRx 处于选择性降低 Lp(a)浓度的前沿,正在进行的研究可能证明这种药物可以降低 Lp(a)介导的残余风险,从而带来心血管获益。

相似文献

[1]
The Role of Antisense Therapies Targeting Lipoprotein(a).

J Cardiovasc Pharmacol. 2021-7-1

[2]
Can Lp(a) Lowering Against Background Statin Therapy Really Reduce Cardiovascular Risk?

Curr Atheroscler Rep. 2019-3-7

[3]
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[4]
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Curr Vasc Pharmacol. 2024

[5]
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Circ J. 2020-4-24

[6]
Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Current Understanding and Future Perspectives.

Cardiovasc Drugs Ther. 2019-12

[7]
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: Present perspectives and future horizons.

Nutr Metab Cardiovasc Dis. 2016-10

[8]
Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials.

Arterioscler Thromb Vasc Biol. 2015-3

[9]
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Curr Opin Endocrinol Diabetes Obes. 2016-4

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

J Intern Med. 2020-1

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[2]
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J Atheroscler Thromb. 2024-10-1

[3]
Lipoprotein a - Lp(a).

Indian Heart J. 2024-3

[4]
Lipoprotein (a) as a Biomarker for Cardiovascular Diseases and Potential New Therapies to Mitigate Risk.

Curr Vasc Pharmacol. 2024

[5]
Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA.

Int J Mol Sci. 2023-10-6

[6]
Targeting the Liver with Nucleic Acid Therapeutics for the Treatment of Systemic Diseases of Liver Origin.

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[7]
Residual risks and evolving atherosclerotic plaques.

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[8]
Impact of Lipoprotein(a) Levels on Perioperative Outcomes in Cardiac Surgery.

Cells. 2021-10-21

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