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Proteomics and Protein Markers |
1 Department of Biotechnology, University of Turku, Turku, Finland.
2 Department of Medicine, University Central Hospital of Turku, Turku, Finland.
3 HyTest Ltd., Turku, Finland.
4 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
aAddress correspondence to this author at: Department of Biotechnology, University of Turku, Tykistökatu 6A, Turku 20520, Finland. Fax 358-2-3338050; e-mail qiqin{at}utu.fi.
Background: In the blood of pregnant women, pregnancy-associated plasma protein A (PAPP-A) is present as a covalent complex with the proform of eosinophil major basic protein (proMBP). Recently, increased serum concentrations of PAPP-A have been found in acute coronary syndromes (ACS). The aim of this study was to investigate whether the circulating PAPP-A in ACS is the same as that in pregnancy.
Methods: We developed two time-resolved immunofluorometric assays based on a relative epitope map constructed by the use of 17 monoclonal antibodies. One assay, which measured total PAPP-A, used two PAPP-A subunit-specific antibodies. The other assay, which measured PAPP-A/proMBP complex, used one proMBP subunit-specific antibody and one PAPP-A subunit-specific antibody. Serum samples from four patients with myocardial infarction (MI), three pregnant women in their first trimester, and one in her third trimester were fractionated by gel filtration on a SuperoseTM 6 precision column. The two assays were used to analyze fractions obtained by gel filtration as well as serum samples serially collected from four other MI patients.
Results: Pregnancy-related PAPP-A was eluted as a single peak with a molecular mass of
700 kDa, whereas ACS-related PAPP-A was also eluted as a single peak but with a molecular mass of
530 kDa. Pregnancy-related PAPP-A was detected equally by the two assays, whereas increased ACS-related PAPP-A was detected only by the assay for total PAPP-A.
Conclusions: Our results provide the first evidence that circulating ACS-related PAPP-A is different from circulating pregnancy-related PAPP-A in that it is not complexed with proMBP. These findings provide a solid foundation for the design of immunoassays to accurately measure atherosclerosis-associated plasma protein A in the circulation.
The following articles in journals at HighWire Press have cited this article:
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C. Gyrup, M. Christiansen, and C. Oxvig Quantification of Proteolytically Active Pregnancy-Associated Plasma Protein-A with an Assay Based on Quenched Fluorescence Clin. Chem., May 1, 2007; 53(5): 947 - 954. [Abstract] [Full Text] [PDF] |
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S. Wittfooth, Q.-P. Qin, J. Lund, I. Tierala, K. Pulkki, H. Takalo, and K. Pettersson Immunofluorometric Point-of-Care Assays for the Detection of Acute Coronary Syndrome-Related Noncomplexed Pregnancy-Associated Plasma Protein A Clin. Chem., September 1, 2006; 52(9): 1794 - 1801. [Abstract] [Full Text] [PDF] |
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S. Fredericks, V. Bertomeu-Gonzalez, I. Petrovic, D. W. Holt, and J. C. Kaski Comment on Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes. Clin. Chem., August 1, 2006; 52(8): 1619 - 1620. [Full Text] [PDF] |
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J. C. Kaski and D. W. Holt Pregnancy-associated plasma protein-A and cardiovascular risk Eur. Heart J., July 2, 2006; 27(14): 1637 - 1639. [Full Text] [PDF] |
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T. Mueller, B. Dieplinger, W. Poelz, and M. Haltmayer Increased Pregnancy-Associated Plasma Protein-A as a Marker for Peripheral Atherosclerosis: Results from the Linz Peripheral Arterial Disease Study Clin. Chem., June 1, 2006; 52(6): 1096 - 1103. [Abstract] [Full Text] [PDF] |
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Q.-P. Qin, S. Kokkala, J. Lund, N. Tamm, X. Qin, M. Lepantalo, and K. Pettersson Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes Clin. Chem., March 1, 2006; 52(3): 398 - 404. [Abstract] [Full Text] [PDF] |
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