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Science 17 November 1989:
Vol. 246. no. 4932, pp. 904 - 910
DOI: 10.1126/science.2530631
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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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G. Lippi and G. Guidi (2000)
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Increased Lipoprotein(a) Is an Important Risk Factor for Venous Thromboembolism in Childhood.
U. Nowak-Gottl, R. Junker, M. Hartmeier, H.-G. Koch, N. Munchow, G. Assmann, and A. von Eckardstein (1999)
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Lipoprotein(a)-Cholesterol and Coronary Heart Disease in the Framingham Heart Study.
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J. Clin. Endocrinol. Metab. 84, 2028-2033
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6-Aminohexanoic Acid as a Chemical Chaperone for Apolipoprotein(a).
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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Lipoprotein(a) in Acromegaly.
P. Maffei, N. Sicolo, and M. Plebani (1999)
Ann Intern Med 130, 537-538
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Lipoprotein(a) and coronary thrombosis and restenosis after stent placement.
A. Wehinger, A. Kastrati, S. Elezi, H. Baum, S. Braun, F.-J. Neumann, and A. Schomig (1999)
J. Am. Coll. Cardiol. 33, 1005-1012
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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)
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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)
J. Am. Coll. Cardiol. 32, 1244-1250
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Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and development of atherosclerosis in apolipoprotein(a) transgenic mice.
X. J. Lou, N. W. Boonmark, F. T. Horrigan, J. L. Degen, and R. M. Lawn (1998)
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Plasma Lipoprotein(a) Is Not a Predictor for Restenosis After Elective High-Pressure Coronary Stenting.
F. Ribichini, G. Steffenino, A. Dellavalle, A. Vado, V. Ferrero, T. Camilla, S. Giubergia, and E. Uslenghi (1998)
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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
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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
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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
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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
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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
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Convergent evolution of apolipoprotein(a) in primates and hedgehog.
R. M. Lawn, K. Schwartz, and L. Patthy (1997)
PNAS 94, 11992-11997
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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
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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
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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
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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
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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
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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
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