Lipoprotein (a). Heterogeneity and biological relevance.
Lipoprotein (a). Heterogeneity and biological relevance.
复制标题
脂蛋白(a)。
DOI：
10.1172/jci114625
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Fless,GM
中科院分区：
文献类型：
--
作者：
Scanu,AM;Fless,GM
脂蛋白（a），或Lp（a），由Kare贝格（1）在25年前发现，至今仍是一个令人着迷的研究课题，因为它被认为与动脉粥样硬化性心血管疾病（ASCVD）有关（2-14），而且它给遗传学家、结构生物学家、生理学家、流行病学家、心脏病学家和临床医生带来了许多挑战。这些挑战之一是阐明这种脂蛋白颗粒所表现出的显着异质性，这是理解其生物学的关键。我们将研究这种异质性的各个方面，并试图提供一个关于Lp（a）的过去和当前知识的全球观点，并确定那些有争议的领域，加强研究工作可能会提供重要的新进展。具有相当宽的沉降系数分布，其中25%的样品具有双峰纹影峰。1984年Flesset等首次对Lp（a）异质性进行了系统的研究。(16)他不仅证实了Harvey和Schultz的发现，而且通过研究个体而不是合并的人类血液样本，还发现Lp（a）表现出个体间和个体内的密度异质性，这种异质性是由蛋白质和脂质组成的差异造成的。在同一项研究中，他们还观察到载脂蛋白（a）[apo（a）]，Lp（a）的特异性标志物，由于电泳迁移率小于，等于或大于低密度脂蛋白（LDL）的蛋白质部分apo B100的电泳迁移率，因此表现出大小异质性。在这些研究中还表明，载脂蛋白（a）的质量有助于Lp（a）的密度，因为较大的载脂蛋白（a）是密度较大的颗粒的主要成分，较小的载脂蛋白（a）优先与低浮力密度的Lp（a）颗粒缔合。这些研究的重要性并不在于-
Lipoprotein (a), or Lp (a),'discovered by KAre Berg (1) more than 25 years ago, remains today a fascinating subject of research both because of its presumed association with athero-sclerotic cardiovascular disease (ASCVD)(2-14) and the many challenges it is offering to geneticists, structural biolo-gists, physiologists, epidemiologists, cardiologists, and clini-cians in general. Among these challenges is the elucidation of the remarkable heterogeneity exhibited by this lipoprotein particle, which is a key for understanding its biology. We will examine the various aspects of this heterogeneity and attempt to provide a global view on past and current knowledge on Lp (a) and identify those controversial areas where intensified research efforts are likely to provide important new advances.Physicochemical basis ofheterogeneity The heterogeneity of Lp (a) went largely unrecognized until Harvie and Schultz (15) reported that their preparations of Lp (a) had a rather broad sedimentation coefficient distribution, and that 25% of them exhibited a bimodal Schlieren peak. The first systematic study on Lp (a) heterogeneity was carried out in 1984by Flesset al.(16), who not only confirmed the findings of Harvey and Schultz but bystudying individual rather than pooled human blood samples also found that Lp (a) exhibits both inter-and intra-individual density heterogeneity, and that this heterogeneity is accounted for by differences in protein and lipid composition. In the same study, they also observed that apolipoprotein (a)[apo (a)], the specific marker of Lp (a), exhibits size heterogeneity owing to species that have electrophoretic mobility either less than, equal to, or greater than that of apo B100, the protein moiety of low density lipoprotein (LDL). In thosestudies it was also shown thatapo (a) mass contributed to Lp (a) density in that the larger apo (a) was the main component of the denser particles and the smaller apo (a) was preferentially associated to Lp (a) particles ofa low buoyant density. The importance of these studies did not be-