Department of Cardiology, Mater Hospital and University of Queensland, Brisbane, Australia.
Department of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Medical University of Graz, Austria.
Atherosclerosis. 2018 Jul;274:16-22. doi: 10.1016/j.atherosclerosis.2018.04.032. Epub 2018 Apr 30.
Lipoprotein (a) (Lp(a)) is a cholesterol-rich lipoprotein known since 1963. In spite of extensive research on Lp(a), there are still numerous gaps in our knowledge relating to its function, biosynthesis and catabolism. One reason for this might be that apo(a), the characteristic glycoprotein of Lp(a), is expressed only in primates. Results from experiments using transgenic animals therefore may need verification in humans. Studies on Lp(a) are also handicapped by the great number of isoforms of apo(a) and the heterogeneity of apo(a)-containing fractions in plasma. Quantification of Lp(a) in the clinical laboratory for a long time has not been standardized. Starting from its discovery, reports accumulated that Lp(a) contributed to the risk of cardiovascular disease (CVD), myocardial infarction (MI) and stroke. Early reports were based on case control studies but in the last decades a great deal of prospective studies have been published that highlight the increased risk for CVD and MI in patients with elevated Lp(a). Final answers to the question of whether Lp(a) is ready for wider clinical use will come from intervention studies with novel selective Lp(a) lowering medications that are currently underway. This article expounds arguments for and against this proposition from currently available data.
脂蛋白 (a) (Lp(a)) 是一种富含胆固醇的脂蛋白,自 1963 年以来就为人所知。尽管对 Lp(a) 进行了广泛的研究,但我们对其功能、生物合成和分解代谢的了解仍然存在许多空白。造成这种情况的原因之一可能是 Lp(a) 的特征糖蛋白 apo(a)仅在灵长类动物中表达。因此,使用转基因动物进行的实验结果可能需要在人类中进行验证。由于 apo(a)的同工型数量众多,以及血浆中含有 apo(a)的部分的异质性,对 Lp(a) 的研究也受到阻碍。长期以来,临床实验室对 Lp(a)的定量检测一直没有标准化。从发现 Lp(a)开始,就有报道称其导致心血管疾病 (CVD)、心肌梗死 (MI) 和中风的风险增加。早期的报告基于病例对照研究,但在过去几十年中,发表了大量的前瞻性研究,强调了 Lp(a 升高的患者 CVD 和 MI 的风险增加。是否准备好将 Lp(a)更广泛地用于临床的最终答案将来自目前正在进行的使用新型选择性 Lp(a)降低药物的干预研究。本文从现有数据出发,阐述了支持和反对这一观点的论据。