Document Detail

Longitudinal analysis of maternal plasma apolipoproteins in pregnancy: a targeted proteomics approach.
MedLine Citation:
PMID:  23059768     Owner:  NLM     Status:  MEDLINE    
Minimally invasive diagnostic tests are needed in obstetrics to identify women at risk for complications during delivery. The apolipoproteins fluctuate in complexity and abundance in maternal plasma during pregnancy and could be incorporated into a blood test to evaluate this risk. The objective of this study was to examine the relative plasma concentrations of apolipoproteins and their biochemically modified subtypes (i.e. proteolytically processed, sialylated, cysteinylated, dimerized) over gestational time using a targeted mass spectrometry approach. Relative abundance of modified and unmodified apolipoproteins A-I, A-II, C-I, C-II, and C-III was determined by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in plasma prospectively collected from 11 gravidas with uncomplicated pregnancies at 4-5 gestational time points per patient. Apolipoproteins were readily identifiable by spectral pattern. Apo C-III(2) and Apo C-III(1) (doubly and singly sialylated Apo C-III subtypes) increased with gestational age (r(2)>0.8). Unmodified Apo A-II, Apo C-I, and Apo C-III(0) showed no correlation (r(2) = 0.01-0.1). Pro-Apo C-II did not increase significantly until third trimester (140 ± 13% of first trimester), but proteolytically cleaved, mature Apo C-II increased in late pregnancy (702 ± 130% of first trimester). Mature Apo C-II represented 6.7 ± 0.9% of total Apo C-II in early gestation and increased to 33 ± 4.5% in third trimester. A label-free, semiquantitative targeted proteomics approach was developed using LTQ-Orbitrap mass spectrometry to confirm the relative quantitative differences observed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in Apo C-III and Apo C-II isoforms between first and third trimesters. Targeted apolipoprotein screening was applied to a cohort of term and preterm patients. Modified Apo A-II isoforms were significantly elevated in plasma from mothers who delivered prematurely relative to term controls (p = 0.02). These results support a role for targeted proteomics profiling approaches in monitoring healthy pregnancies and assessing risk of adverse obstetric outcomes.
Shannon K Flood-Nichols; Deborah Tinnemore; Mark A Wingerd; Ali I Abu-Alya; Peter G Napolitano; Jonathan D Stallings; Danielle L Ippolito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-10
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  12     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-06-24     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  55-64     Citation Subset:  IM    
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MeSH Terms
Apolipoprotein A-II / blood
Apolipoprotein C-I / blood
Apolipoprotein C-II / blood
Apolipoprotein C-III / blood
Apolipoproteins / blood*
Biological Markers / blood
Gestational Age*
Longitudinal Studies
Mass Spectrometry
Pregnancy Outcome*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reg. No./Substance:
0/Apolipoprotein A-II; 0/Apolipoprotein C-I; 0/Apolipoprotein C-II; 0/Apolipoprotein C-III; 0/Apolipoproteins; 0/Biological Markers

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