Department of Clinical Sciences (DISCO), Polytechnic University of Marche, Marche, Italy.
Department of Life and Environmental Sciences (DISVA), Polytechnic University of Marche, Marche, Italy.
J Cell Physiol. 2018 Apr;233(4):2966-2981. doi: 10.1002/jcp.26050. Epub 2017 Jul 11.
Lipoprotein(a) Lp(a) is a cholesterol-rich, LDL-like particle that is independently associated with an increased risk for ischemic heart disease, atherosclerosis, thrombosis, and stroke. Genetic variation in the Lp(a) locus and some other genes related to Lp(a) synthesis and metabolism play a critical role in regulating plasma Lp(a) levels. The pathophysiological potential of Lp(a) is related to proatherogenic and prothrombotic effects on the vasculature. Different molecular mechanisms underlying the atherothrombotic potential of Lp(a), free apolipoprotein(a), and oxidized-Lp(a) have been proposed. However, plasma Lp(a) assay is complicated by problems associated with quantification and standardization owing to the polymorphic nature of this lipoprotein. This review has focused on the physicochemical properties of Lp(a), the genetic aspects of Lp(a), the need for accurate determination of Lp(a), the synthesis, and recent findings on metabolism of Lp(a). Lastly, the patho-physiological mechanisms by which Lp(a) may increase athero-thrombosis and an overview on the therapeutic modalities to interfere with Lp(a) are summarized.
脂蛋白(a)[Lp(a)]是一种富含胆固醇的 LDL 样颗粒,它与缺血性心脏病、动脉粥样硬化、血栓形成和中风的风险增加独立相关。Lp(a)基因座和一些与 Lp(a)合成和代谢相关的其他基因的遗传变异在调节血浆 Lp(a)水平方面起着关键作用。Lp(a)的病理生理学潜能与对血管的促动脉粥样硬化和促血栓形成作用有关。已经提出了 Lp(a)、游离载脂蛋白(a)和氧化型 Lp(a)的动脉血栓形成潜能的不同分子机制。然而,由于这种脂蛋白的多态性,血浆 Lp(a)测定受到与定量和标准化相关的问题的困扰。本综述重点介绍了 Lp(a)的理化特性、Lp(a)的遗传方面、准确测定 Lp(a)的必要性、合成以及最近关于 Lp(a)代谢的发现。最后,总结了 Lp(a)增加动脉粥样硬化血栓形成的病理生理学机制以及干扰 Lp(a)的治疗方式概述。