title: Alterations to the maternal circulating proteome after preeclampsia.
abstract: OBJECTIVE
  The long-term maternal cardiovascular and metabolic implications associated with preeclampsia (PE) include risk of hypertension, heart disease, and metabolic syndrome. The objective of this study was to investigate if a recent history of PE was associated with detectable alterations in the circulating maternal proteome.
  
  
  METHODS
  Six-month postpartum plasma from women with a history of PE (n = 12) and women with uncomplicated obstetrical history (n = 12) were used for analysis. Depleted maternal plasma was analyzed by label-free liquid chromatography-mass spectrometry assay. Identified peptides were searched against the International Protein Index human database version 3.87. Exponentially modified protein abundance indices were used for comparison. Results were analyzed using pathway analysis software.
  
  
  RESULTS
  A total of 126 eligible peptides were identified for analysis; 3 peptides were differentially expressed in the PE proteome, and an additional 5 peptides were unique to control subjects and 7 to PE subjects. PE peptide profiles were more strongly associated with markers of coagulation and complement activation compared to controls and mapped more significantly to cardiovascular disease (CVD) functions. Stratification of subjects by low (<39%) and high (≥39%) lifetime risk of CVD rather than by diagnosis produced similar findings. Comparison of controls (n = 6) to PE subjects (n = 6) without traditional cardiovascular risk factors found that while similar for body mass indices, blood pressure, and fasting lipid profiles at 6 months postpartum, PE peptide profiles continued to display stronger associations for coagulation and CVD functions. Global network analysis found that unique peptides to low-risk PE subjects were associated with cardiac infarction, CVD, and organismal injury and abnormalities.
  
  
  CONCLUSIONS
  Markers of CVD risk and progression are evident in the maternal circulating proteome 6 months postpartum after PE. Augmentations in circulating peptide profiles occur in patients with previous PE who otherwise do not have clinically measurable cardiovascular risk factors. Our data highlight the need for the implementation of postpartum prevention programs in the PE population and identifies molecules that may be targeted for screening or therapeutic benefit.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Malia Su-Qin
authors.initials: MS
authors.lastname: Murphy
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX.
authors.forename: Egle
authors.initials: E
authors.lastname: Bytautiene
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX.
authors.forename: George
authors.initials: G
authors.lastname: Saade
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Department of Obstetrics and Gynecology, Kingston General Hospital, Kingston, Ontario, Canada. Electronic address: gns@queensu.ca.
authors.forename: Graeme Neil
authors.initials: GN
authors.lastname: Smith
mesh_terms: D048948:14-3-3 Proteins / Q000097:blood; D000328:Adult; D001798:Blood Proteins / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood; D016022:Case-Control Studies; D053454:Caspase 12 / Q000097:blood; D003598:Cytoskeletal Proteins / Q000097:blood; D005260:Female; D006801:Humans; D049590:Postpartum Period / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D020543:Proteome / Q000032:analysis*; D018570:Risk Assessment
chemical_list: D048948:14-3-3 Proteins; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D020543:Proteome; C572235:YWHAZ protein, human; C506444:CASP12 protein, human; D053454:Caspase 12
keywords: cardiovascular risk; maternal health; preeclampsia; proteome