The complex pro-atherosclerotic role of lipoprotein(a): a multiplicity of cellular targets.

IF 4.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI:10.1097/MOL.0000000000001000
Julia M Assini, Michael B Boffa, Marlys L Koschinsky
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引用次数: 0

Abstract

Purpose of review: Elevated plasma lipoprotein(a) (Lp(a)) is a causal and independent risk factor for atherosclerotic cardiovascular disease; therefore, understanding the fundamental mechanisms underlying Lp(a)-mediated pathogenesis is of significant clinical importance. This review summarizes recent advances in understanding the precise cellular targets of Lp(a) in atherogenesis, uncovering potential therapeutic avenues worth exploring.

Recent findings: Genetic evidence reveals that Lp(a) is six-fold more atherogenic per particle than LDL, and clinical imaging studies show increased atherosclerotic plaque burden and severity in patients with elevated Lp(a). A novel study using human monocytes uncovered diacylglycerols and lysophosphatidic acid as lipid species that contribute to the pro-inflammatory impacts of Lp(a), independent of the known pro-inflammatory oxidized phospholipids. The identification of a novel cell-surface receptor on endothelial cells involved in Lp(a) uptake offers another exploratory direction in vascular cells involved in atherosclerosis. Several studies have also pointed to accelerated coagulation as a potential target of Lp(a), involving Lp(a)-mediated impacts on platelet aggregation and monocyte tissue factor expression.

Summary: An understanding of these cell-specific targets of Lp(a) in atherogenesis will aid the Lp(a) field in identifying novel therapeutic targets for patients with elevated Lp(a), for whom few available therapeutic strategies currently exist.

脂蛋白的复杂促动脉粥样硬化作用(a):细胞靶点的多样性。
综述目的:血浆脂蛋白(a)升高(Lp(a))是动脉粥样硬化性心血管疾病的一个因果和独立危险因素;因此,了解Lp(a)介导的发病机制的基本机制具有重要的临床意义。本文综述了在了解Lp(a)在动脉粥样硬化中的精确细胞靶点方面的最新进展,揭示了值得探索的潜在治疗途径。最近发现:遗传证据显示,每颗粒Lp(a)的致动脉粥样硬化性是LDL的6倍,临床影像学研究显示Lp(a)升高的患者动脉粥样硬化斑块负担和严重程度增加。一项利用人类单核细胞的新研究发现,二酰基甘油和溶血磷脂酸作为脂类有助于Lp(A)的促炎作用,独立于已知的促炎氧化磷脂。在参与Lp(a)摄取的内皮细胞上发现一种新的细胞表面受体,为研究参与动脉粥样硬化的血管细胞提供了另一个探索方向。一些研究也指出加速凝血是Lp(a)的潜在靶点,涉及Lp(a)介导的对血小板聚集和单核细胞组织因子表达的影响。摘要:了解动脉粥样硬化中Lp(a)的这些细胞特异性靶点将有助于Lp(a)领域为Lp(a)升高的患者确定新的治疗靶点,目前很少有可用的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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