Pregnancy-associated plasma protein-A (PAPP-A) and the proform of the eosinophil major basic protein (ProMBP) are associated with increased risk of death in heart failure patients

Author(s):  
Maja Dembic ◽  
Paula L. Hedley ◽  
Christian Torp-Pedersen ◽  
Lars Køber ◽  
Michael Christiansen
2002 ◽  
Vol 278 (4) ◽  
pp. 2106-2117 ◽  
Author(s):  
Michael T. Overgaard ◽  
Esben S. Sørensen ◽  
Damian Stachowiak ◽  
Henning B. Boldt ◽  
Lene Kristensen ◽  
...  

2000 ◽  
Vol 275 (40) ◽  
pp. 31128-31133 ◽  
Author(s):  
Michael T. Overgaard ◽  
Jesper Haaning ◽  
Henning B. Boldt ◽  
Inger M. Olsen ◽  
Lisbeth S. Laursen ◽  
...  

2007 ◽  
Vol 53 (5) ◽  
pp. 947-954 ◽  
Author(s):  
Claus Gyrup ◽  
Michael Christiansen ◽  
Claus Oxvig

Abstract Background: Maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome. In pregnancy, PAPP-A primarily circulates as a covalent 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. At term, however, ∼1% of PAPP-A exists as an active, uncomplexed dimer with proteolytic activity directed specifically toward insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5. No assays have been developed that allow quantification of PAPP-A proteolytic activity. Methods: We developed a sensitive and specific immunocapture assay for PAPP-A activity based on intramolecular quenched fluorescence. We used a 26-residue synthetic peptide derived from IGFBP-4 in which specific positions on each side of the PAPP-A cleavage site were substituted with 3-nitrotyrosine and o-aminobenzoic acid. Results: The assay detected the activity of recombinant PAPP-A as well as PAPP-A in serum samples from pregnant women. The limit of detection (mean signal of blank plus 3 SD) of the active PAPP-A subunit was 13 pmol/L, and the intra- and interassay CVs were <10% and <15%, respectively. Interestingly, the fraction of active PAPP-A decreased gradually from week 7 to week 19 of pregnancy. Conclusions: This method allows the measurement of PAPP-A enzymatic activity and because of its specificity it is relevant to the study of the biological function of PAPP-A. The method may also be useful in the diagnosis of pregnancy disorders.


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