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Science 17 November 1989:
Vol. 246. no. 4932, pp. 904 - 910
DOI: 10.1126/science.2530631

Articles

Science, Vol 246, Issue 4932, 904-910
Copyright © 1989 by American Association for the Advancement of Science


articles

The mysteries of lipoprotein(a)

G Utermann

Institute for Medical Biology and Genetics, University of Innsbruck, Austria.

Lipoprotein(a) [Lp(a)] is a macromolecular complex found in human plasma that combines structural elements from the lipoprotein and blood clotting systems and that is associated with premature coronary heart disease and stroke. It is assembled from low-density lipoprotein (LDL) and a large hydrophilic glycoprotein called apolipoprotein(a) [apo(a)], which is homologous to the protease zymogen plasminogen. Plasma Lp(a) concentrations vary 1000-fold between individuals and represent a continuous quantitative genetic trait with a skewed distribution in Caucasian populations. Variation in the hypervariable apo(a) gene on chromosome 6q2.6-q2.7 and interaction of apo(a) alleles with defective LDL-receptor genes explain a large fraction of the variability of plasma Lp(a) concentrations. Though of high theoretical and practical interest, many aspects of the metabolism, function, evolution, and regulation of plasma concentrations of Lp(a) are presently unknown, controversial, or mysterious.


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J. Lipid Res. 41, 1110-1117
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K. Miwa, K. Nakagawa, N. Yoshida, Y. Taguchi, and H. Inoue (2000)
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A. Kagawa, H. Azuma, M. Akaike, Y. Kanagawa, and T. Matsumoto (1999)
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Increased Prevalence of Smaller and Denser LDL Particles in Asian Indians.
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D. Boffelli, D. A. Zajchowski, Z. Yang, and R. M. Lawn (1999)
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J. Wang and A. L. White (1999)
J. Biol. Chem. 274, 12883-12889
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M. Leonsson, J. Oscarsson, I. Bosaeus, B. K. Lundgren, G. Johannsson, O. Wiklund, and B. A. Bengtsson (1999)
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Effect of Cardiopulmonary Bypass and Heparin on Plasma Levels of Lp(a) and Apo(a) Fragments.
V. Mooser, F. Tinguely, P. Fontana, V. Lenain, M. Vaglio, P. Ruchat, L. K. von Segesser, S. M. Marcovina, M. Markert, R. Darioli, et al. (1999)
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Dose-Dependent Inverse Relationship Between Alcohol Consumption and Serum Lp(a) Levels in Black African Males.
P. Fontana, V. Mooser, P. Bovet, C. Shamlaye, B. Burnand, V. Lenain, S. M. Marcovina, W. Riesen, and R. Darioli (1999)
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Lipoprotein(a) in Acromegaly.
P. Maffei, N. Sicolo, and M. Plebani (1999)
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Lipoprotein(a) and coronary thrombosis and restenosis after stent placement.
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Molecular Basis of the Interaction between Plasma Platelet-activating Factor Acetylhydrolase and Low Density Lipoprotein.
D. M. Stafforini, L. W. Tjoelker, S. P. A. McCormick, D. Vaitkus, T. M. McIntyre, P. W. Gray, S. G. Young, and S. M. Prescott (1999)
J. Biol. Chem. 274, 7018-7024
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Identification of Megalin/gp330 as a Receptor for Lipoprotein(a) In Vitro.
A. Niemeier, T. Willnow, H. Dieplinger, C. Jacobsen, N. Meyer, J. Hilpert, and U. Beisiegel (1999)
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Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway.
A. L. White, B. Guerra, J. Wang, and R. E. Lanford (1999)
J. Lipid Res. 40, 275-286
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{beta}2 glycoprotein I containing immune-complexes in lupus patients: association with thrombocytopenia and lipoprotein (a) levels.
J George, B Gilburd, P Langevitz, Y Levy, R Nezlin, D Harats, and Y Shoenfeld (1999)
Lupus 8, 116-120
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The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease.
E. Sbarouni, Z. S. Kyriakides, and D. T. Kremastinos (1998)
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   Abstract »    Full Text »    PDF »
Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors.
S. Donazzan, D. Monti, D. Mari, S. Martini, C. Gabelli, M. D. Vestra, L. Previato, M. Guido, S. Pigozzo, I. Cortella, et al. (1998)
FASEB J 12, 433-437
   Abstract »    Full Text »
Increased Degradation of Lipoprotein(a) in Atherosclerotic Compared With Nonlesioned Aortic Intima–Inner Media of Rabbits : In Vivo Evidence That Lipoprotein(a) May Contribute to Foam Cell Formation.
L. B. Nielsen, K. Juul, and B. G. Nordestgaard (1998)
Arterioscler. Thromb. Vasc. Biol. 18, 641-649
   Abstract »    Full Text »    PDF »
Alcohol Withdrawal–Induced Change in Lipoprotein(a) : Association With the Growth Hormone/Insulin-like Growth Factor-I (IGF-I)/IGF-Binding Protein-1 (IGFBP-1) Axis.
M. Paassilta, K. Kervinen, M. Linnaluoto, and Y. A. Kesaniemi (1998)
Arterioscler. Thromb. Vasc. Biol. 18, 650-654
   Abstract »    Full Text »    PDF »
Apolipoprotein(a) Gene Enhancer Resides within a LINE Element.
Z. Yang, D. Boffelli, N. Boonmark, K. Schwartz, and R. Lawn (1998)
J. Biol. Chem. 273, 891-897
   Abstract »    Full Text »    PDF »
Apolipoprotein(a) Yeast Artificial Chromosome Transgenic Rabbits. LIPOPROTEIN(a) ASSEMBLY WITH HUMAN AND RABBIT APOLIPOPROTEIN B.
D. Rouy, N. Duverger, S. D. Lin, F. Emmanuel, L.-M. Houdebine, P. Denefle, C. Viglietta, E. Gong, E. M. Rubin, and S. D. Hughes (1998)
J. Biol. Chem. 273, 1247-1251
   Abstract »    Full Text »    PDF »
Thrombosis and Hemostasis in Cardiology: Review of Pathophysiology and Clinical Practice (Part I).
W. F. Baker JR (1998)
Clinical and Applied Thrombosis/Hemostasis 4, 51-75
   Abstract »    PDF »
Oral 17{beta}-Estradiol Continuously Combined with Dydrogesterone Lowers Serum Lipoprotein(a) Concentrations in Healthy Postmenopausal Women.
V. Mijatovic, P. Kenemans, J. C. Netelenbos, E. R. A. Peters-Muller, G. J. van Kamp, G. A. Voetberg, P. H. M. van de Weijer, and M. J. van der Mooren (1997)
J. Clin. Endocrinol. Metab. 82, 3543-3547
   Abstract »    Full Text »    PDF »
Convergent evolution of apolipoprotein(a) in primates and hedgehog.
R. M. Lawn, K. Schwartz, and L. Patthy (1997)
PNAS 94, 11992-11997
   Abstract »    Full Text »    PDF »
Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease.
W.-K. Min, J. O. Lee, and J. W. Huh (1997)
Clin. Chem. 43, 1891-1895
   Abstract »    Full Text »    PDF »
Transgenic Mice Expressing Human ApoB95 and ApoB97. EVIDENCE THAT SEQUENCES WITHIN THE CARBOXYL-TERMINAL PORTION OF HUMAN apoB100 ARE IMPORTANT FOR THE ASSEMBLY OF LIPOPROTEIN(a).
S. P. A. McCormick, J. K. Ng, C. M. Cham, S. Taylor, S. M. Marcovina, J. P. Segrest, R. E. Hammer, and S. G. Young (1997)
J. Biol. Chem. 272, 23616-23622
   Abstract »    Full Text »    PDF »
Effects of Estrus Cycle, Ovariectomy, and Treatment with Estrogen, Tamoxifen, and Progesterone on Apolipoprotein(a) Gene Expression in Transgenic Mice.
B. R. Zysow, K. Kauser, R. M. Lawn, and G. M. Rubanyi (1997)
Arterioscler. Thromb. Vasc. Biol. 17, 1741-1745
   Abstract »    Full Text »
Lipoprotein(a) Is a Potent Chemoattractant for Human Peripheral Monocytes.
T. Syrovets, J. Thillet, M. J. Chapman, and T. Simmet (1997)
Blood 90, 2027-2036
   Abstract »    Full Text »    PDF »
Novel Interaction of Apolipoprotein(a) With beta -2 Glycoprotein I Mediated by the Kringle IV Domain.
S. Kochl, F. Fresser, E. Lobentanz, G. Baier, and G. Utermann (1997)
Blood 90, 1482-1489
   Abstract »    Full Text »    PDF »
Association of Serum Lipoprotein(a) Levels and Apolipoprotein(a) Size Polymorphism With Target-Organ Damage in Arterial Hypertension.
L. A. Sechi, F. Kronenberg, S. De Carli, E. Falleti, L. Zingaro, C. Catena, G. Utermann, and E. Bartoli (1997)
JAMA 277, 1689-1695
   Abstract »    PDF »
Lipoprotein (a): Its Role in Childhood Thromboembolism.
U. Nowak-Gottl, O. Debus, M. Findeisen, R. Kassenbohmer, H. G. Koch, H. Pollmann, C. Postler, P. Weber, and H. Vielhaber (1997)
Pediatrics 99, e11
   Abstract »    Full Text »    PDF »
Expression of a Recombinant Apolipoprotein(a) in HepG2 Cells. EVIDENCE FOR INTRACELLULAR ASSEMBLY OF LIPOPROTEIN(a).
D. K. Bonen, A. M.L. Hausman, C. Hadjiagapiou, S. F. Skarosi, and N. O. Davidson (1997)
J. Biol. Chem. 272, 5659-5667
   Abstract »    Full Text »    PDF »
Influence of Allelic Variation on Apolipoprotein(a) Folding in the Endoplasmic Reticulum.
A. L. White, B. Guerra, and R. E. Lanford (1997)
J. Biol. Chem. 272, 5048-5055
   Abstract »    Full Text »    PDF »
A Prospective Case-Control Study of Lipoprotein(a) Levels and Apo(a) Size and Risk of Coronary Heart Disease in Stanford Five-City Project Participants.
S. H. Wild, S. P. Fortmann, and S. M. Marcovina (1997)
Arterioscler. Thromb. Vasc. Biol. 17, 239-245
   Abstract »    Full Text »
Platelet Integrin {alpha}IIbß3 (GPIIb-IIIa) Is Not Implicated in the Binding of LDL to Intact Resting Platelets.
J. Pedreno, R. Fernandez, C. Cullare, A. Barcelo, M. A. Elorza, and C. de Castellarnau (1997)
Arterioscler. Thromb. Vasc. Biol. 17, 156-163
   Abstract »    Full Text »
The Binding Activity of the Macrophage Lipoprotein(a)/Apolipoprotein(a) Receptor Is Induced by Cholesterol via a Post-translational Mechanism and Recognizes Distinct Kringle Domains on Apolipoprotein(a).
G. A. Keesler, B. R. Gabel, C. M. Devlin, M. L. Koschinsky, and I. Tabas (1996)
J. Biol. Chem. 271, 32096-32104
   Abstract »    Full Text »    PDF »
The Number of Identical Kringle IV Repeats in Apolipoprotein(a) Affects Its Processing and Secretion by HepG2 Cells.
C. Brunner, E.-M. Lobentanz, A. Petho-Schramm, A. Ernst, C. Kang, H. Dieplinger, H.-J. Muller, and G. Utermann (1996)
J. Biol. Chem. 271, 32403-32410
   Abstract »    Full Text »    PDF »



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