Molecular distinction of circulating pregnancy-associated plasma protein A in myocardial infarction and pregnancy.
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 Superose 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 approximately 700 kDa, whereas ACS-related PAPP-A was also eluted as a single peak but with a molecular mass of approximately 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.
Qin
Qiu-Ping
QP
Department of Biotechnology, University of Turku, Turku 20520, Finland. qiqin@utu.fi
Kokkala
Saara
S
Lund
Juha
J
Tamm
Natalia
N
Voipio-Pulkki
Liisa-Maria
LM
Pettersson
Kim
K
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D002850:Chromatography, Gel; D018604:Epitope Mapping; D005260:Female; D005865:Gestational Age; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D011266:Pregnancy-Associated Plasma Protein-A