Lipoprotein(a) consists of a low-density lipoprotein containing apolipoprotein (apo) B-100 and of the genetically polymorphic apo(a). It is not known where and how lipoprotein(a) is assembled and whether there exists a precursor for lipoprotein(a). We have determined the phenotype, concentration, and distribution of apo(a) in plasma from patients with lipoprotein lipase (LPL) deficiency (type I hyperlipoproteinemia, n = 14), in apo E 2/2 homozygotes with type III hyperlipoproteinemia (n = 12) and in controls (n = 16). In the two genetic conditions, there is grossly impaired catabolic conversion of apo B-100-containing precursor lipoproteins to low-density lipoproteins. Considering apo(a) type, the plasma concentration of apo(a) was normal in type III patients but significantly reduced in LPL deficiency. Despite the defects in the catabolism of other apo B-containing lipoproteins, the distribution of apo(a) was only moderately affected in both metabolic disorders, with 66.7% (type I) and 74.7% (type III) being present as the characteristic lipoprotein(a) in the density range of 1.05-1.125 g/ml (controls 81.6%). The remainder was distributed between the triglyceride-rich lipoproteins (type I 12.4%, type III 8.5%, controls 4.7%) and the lipid-poor bottom fraction (type I 19.3%, type III 15.3%, controls 12.6%). In all conditions most apo(a) (57-88%) dissociated from the triglyceride-rich lipoproteins upon recentrifugation and was recovered as lipoprotein(a). These data suggest that lipoprotein(a) is not generated from a triglyceride-rich precursor. Lipoprotein(a) may be secreted directly into plasma or may be formed by preferential binding of secreted apo(a) to existing low-density lipoprotein.
C Sandholzer, G Feussner, J Brunzell, G Utermann
Title and authors | Publication | Year |
---|---|---|
Apolipoprotein(a) is the Product of a Pseudogene: Implications for the Pathophysiology of Lipoprotein(a)
GD Sloop, G Pop, JJ Weidman, JA Cyr |
Cureus | 2018 |
Lipoprotein(a) and apolipoprotein(a) isoform size: Associations with angiographic extent and severity of coronary artery disease, and carotid artery plaque
EM Ooi, KL Ellis, PH Barrett, GF Watts, J Hung, JP Beilby, PL Thompson, P Stobie, BM McQuillan |
Atherosclerosis | 2018 |
Structure, function, and genetics of lipoprotein (a)
K Schmidt, A Noureen, F Kronenberg, G Utermann |
Journal of lipid research | 2016 |
Methods in Enzymology
JD Stone, AS Chervin, DH Aggen, DM Kranz |
Protein Engineering for Therapeutics Part B | 2012 |
Advances in Clinical Chemistry
M Mahler |
Advances in Clinical Chemistry Volume 54 | 2011 |
Lipoprotein(a) and the risk of thromboembolism in Thai children
N Sirachainan, C Chaiyong, A Visudtibhan, W Sasanakul, S Osatakul, P Wongwerawattanakoon, P Kadegasem, A Chuansumrit |
Thrombosis Research | 2011 |
Evidence of dependence of lipoprotein(a) on triglyceride and high-density lipoprotein metabolism
M Konerman, K Kulkarni, PP Toth, SR Jones |
Journal of Clinical Lipidology | 2011 |
Apolipoprotein B-100-Containing Lipoprotein Metabolism in Subjects With Lipoprotein Lipase Gene Mutations
EM Ooi, BS Russell, E Olson, SZ Sun, MR Diffenderfer, AH Lichtenstein, L Keilson, PH Barrett, EJ Schaefer, DL Sprecher |
Arteriosclerosis, thrombosis, and vascular biology | 2011 |
Lipoprotein(a): an independent risk factor for ischemic heart disease that is dependent on triglycerides in subjects with type 2 diabetes mellitus
A Albahrani, M Alkindi, E Marks, S Alyahyaee, A Shenkin |
Lipids in Health and Disease | 2007 |
Postprandial Lipoprotein(a) Is Affected Differently by Specific Individual Dietary Fatty Acids in Healthy Young Men
T Tholstrup, S Samman |
The Journal of nutrition | 2004 |
Isolation, quantitation, and characterization of a stable complex formed by Lp[a] binding to triglyceride-rich lipoproteins
JW Gaubatz, RC Hoogeveen, AS Hoffman, KG Ghazzaly, HJ Pownall, J Guevara, ML Koschinsky, JD Morrisett |
Journal of lipid research | 2001 |
Association of Lp(a) rather than integrally-bound apo(a) with triglyceride-rich lipoproteins of human subjects
C Marcoux |
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | 1997 |
Statin therapy in a kindred with both apolipoprotein B and low density lipoprotein receptor gene defects
FJ Raal, G Pilcher, DC Rubinsztein, A Lingenhel, G Utermann |
Atherosclerosis | 1997 |
Lipoprotein(a) in renal disease
F Kronenberg, G Utermann, H Dieplinger |
American Journal of Kidney Diseases | 1996 |
Lipoprotein(a) is increased in triglyceride-rich lipoproteins in men with coronary heart disease, but does not change acutely following oral fat ingestion
F Hoppichler, HG Kraft, C Sandholzer, M Lechleitner, JR Patsch, G Utermann |
Atherosclerosis | 1996 |
Interrelationship of triglyceride-rich lipoproteins, serum lipoprotein(a) concentration and apolipoprotein(a) size
M SentÍ, J Pedro-Botet, J Rubiés-Prat, J Marrugat |
Scandinavian Journal of Clinical & Laboratory Investigation | 1996 |
Lipoprotein(a) in Health and Disease
F Kronenberg, A Steinmetz, GM Kostner, H Dieplinger |
Critical Reviews in Clinical Laboratory Sciences | 1996 |
Atherogenesis in transgenic mice with human apolipoprotein B and lipoprotein (a)
MJ Callow, J Verstuyft, R Tangirala, W Palinski, EM Rubin |
Journal of Clinical Investigation | 1995 |
Effect of hypertriglyceridaemia on lipoprotein (a) serum concentrations
T Walek, AV Eckardstein, H Schulte, G Assmann |
European Journal of Clinical Investigation | 1995 |
Lipoprotein (a) in patients with hyperlipidaemia
W Bartens, DJ Rader, G Talley, HB Brewer |
European Journal of Clinical Investigation | 1995 |
The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction
VN Trieu, U Olsson, WJ McConathy |
Biochemical Journal | 1995 |
Lipoprotein lipase does not affect lipoprotein (a) levels in normotriglyceridemic patients
RD Santos, C Vinagre, RC Maranhão |
International Journal of Cardiology | 1995 |
Site-specific Mutagenesis Demonstrates That Cysteine 4326 of Apolipoprotein B Is Required for Covalent Linkage with Apolipoprotein(a) in Vivo
MJ Callow, EM Rubin |
The Journal of biological chemistry | 1995 |
Dose-Response Relationships of Serum Lipid Measurements With the Extent of Coronary Stenosis: Strong, Independent, and Comprehensive
I Bolibar, SG Thompson, A von Eckardstein, M Sandkamp, G Assmann |
Arteriosclerosis, thrombosis, and vascular biology | 1995 |
Apolipoprotein (a) phenotypes and lipoprotein (a) concentrations in patients with type III hyperlipoproteinaemia
G Feussner, V Feussner, R Ziegler |
Journal of Internal Medicine | 1994 |
Decreased plasma levels of lipoprotein(a) in patients with hypertriglyceridemia
W Bartens, DJ Rader, G Talley, HB Brewer |
Atherosclerosis | 1994 |
Lipoprotein (a): implication in atherothrombosis
MJ Chapman, T Huby, F Nigon, J Thillet |
Atherosclerosis | 1994 |
Structure and Possible biological roles of Lp(a)
I Karmansky, N Gruener |
Clinical Biochemistry | 1994 |
High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection": The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein
S Frank, K Krasznai, S Durovic, EM Lobentanz, H Dieplinger, E Wagner, K Zatloukal, M Cotten, G Utermann |
Biochemistry | 1994 |
Apolipoprotein(a) phenotypes predict the risk for carotid atherosclerosis in patients with end-stage renal disease
F Kronenberg, H Kathrein, P König, U Neyer, W Sturm, K Lhotta, E Gröchenig, G Utermann, H Dieplinger |
Arteriosclerosis Thrombosis and Vascular Biology | 1994 |
Principles and Treatment of Lipoprotein Disorders
G Schettler, AJ Habenicht |
1994 | |
Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia implication for lipoprotein(a) metabolism
G Lindahl, F Mailly, S Humphries, M Seed |
The Clinical Investigator | 1994 |
Lipoprotein(a) : new insights into an atherogenic lipoprotein
W Bartens, C Wanner |
The Clinical Investigator | 1994 |
Cellular Metabolism of the Arterial Wall and Central Nervous System
G Schettler, H Greten, AJ Habenicht |
1993 | |
Relation of cardiovascular risk factors to atherosclerosis in type III hyperlipoproteinemia
G Feussner, A Wagner, R Ziegler |
Human Genetics | 1993 |