Lipoprotein(a): structural implications for pathophysiology
- 1 March 1997
- journal article
- review article
- Published by Springer Nature in International Journal of Clinical and Laboratory Research
- Vol. 27 (1), 14-23
- https://doi.org/10.1007/bf02827238
Abstract
The assembly between a low-density lipoprotein particle and apolipoprotein(a), a highly carbohydraterich protein, gives origin to a peculiar class of lipoproteins, only found in the hedgehog, primates, and humans, termed lipoprotein(a). Apolipoprotein(a), which shares a high degree of sequence homology with the fibrinolytic proenzyme plasminogen, is linked to the apolipoprotein B-100 component of low-density lipoprotein via a disulfide bond and confers distinct biochemical and metabolic properties to lipoprotein(a). Because of its peculiar structural features and the observed correlation between high lipoprotein(a) levels and the development of a variety of atherosclerotic disorders, this lipoprotein has become the focus of an intense research effort. Although accumulation of lipoprotein(a) in the vessel wall at sites of vascular injury has been clearly evidenced, the mechanism(s) by which lipoprotein(a) exerts its pathogenic effect in this milieu remain largely unknown. It has been hypothesized that the pathological effect of lipoprotein(a) is related either to its similarity to low-density lipoprotein (i.e., a pro-atherogenic effect) or to the apolipoprotein(a) similarity to plasminogen (i.e., a pro-thrombotic/anti-fibrinolytic effect). However, it is probable that both components contribute to the pathogenicity of lipoprotein(a). The fact that lipoprotein(a) levels are largely genetically determined, varying widely among individuals and racial groups, adds additional elements to the scientific interest that surrounds this lipoprotein. Both clinical and biochemical studies of lipoprotein(a) have been complicated by the high degree of structural heterogeneity of apolipoprotein(a), which is considered the most polymorphic protein in human plasma. Our aim in this paper is to provide an overview of the most salient structural features of lipoprotein(a) and their possible pathophysiological implications.Keywords
This publication has 105 references indexed in Scilit:
- Familial Hypobetalipoproteinemia Is Not Associated With Low Levels of Lipoprotein(a)Arteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Binding of recombinant apolipoprotein(a) to extracellular matrix proteins.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1994
- Heterogeneous lipoprotein (a) size isoforms differ by their interaction with the low density lipoprotein receptor and the low density lipoprotein receptor‐related protein/α2‐macroglobulin receptorFEBS Letters, 1993
- Identification of 34 Apolipoprotein(a) Isoforms: Differential Expression of Apolipoprotein(a) Alleles between American Blacks and WhitesBiochemical and Biophysical Research Communications, 1993
- Lipoprotein(a) and accelerated coronary artery disease in cardiac transplant recipientsThe Lancet, 1992
- Isolation and characterization of two sub-species of Lp(a), one containing apo E and one free of apo EBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1992
- Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese.Stroke, 1991
- cDNA sequence of human apolipoprotein(a) is homologous to plasminogenNature, 1987
- Lipoprotein(a) as a strong indicator for cerebrovascular disease.Stroke, 1986
- PAPER V: Myocardial Infarction and an Extra Pre‐beta Lipoprotein FractionActa Medica Scandinavica, 1972