| Longitudinal Analysis of Maternal Plasma Apolipoproteins in Pregnancy: A Targeted Proteomics Approach. | |
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MedLine Citation:
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PMID: 23059768 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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, sialyated, cysteinylated, dimerized) over gestational time using a targeted mass spectrometry approach. Relative abundance of modified and unmodified apolipoproteins AI, AII, CI, CII, and CIII was determined by surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOF MS) 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, semi-quantitative targeted proteomics approach was developed using LTQ-Orbitrap mass spectrometry to confirm the relative quantitative differences in Apo C-III and Apo C-II subtypes between first and third trimesters observed by SELDI-TOF MS. 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 to monitor healthy pregnancies and assess risk of adverse obstetric outcomes. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-10-10 |
Journal Detail:
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Title: Molecular & cellular proteomics : MCP Volume: - ISSN: 1535-9484 ISO Abbreviation: Mol. Cell Proteomics Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101125647 Medline TA: Mol Cell Proteomics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Madigan Healthcare System, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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