title: Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice.
abstract: OBJECTIVE
  Preeclampsia is associated with long-term adverse maternal health, such as cardiovascular and metabolic diseases. The objective of this study was to determine whether preeclampsia in a well-characterized animal model that was induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) results in alterations in the maternal circulating proteome that persist long after delivery.
  
  
  METHODS
  CD-1 mice at day 8 of gestation were injected with adenovirus that carried sFlt1 or the murine immunoglobulin G2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography-mass spectrometry assay. The tandem mass spectrometry data were searched against a mouse database, and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool. Results were analyzed with ingenuity pathways analysis. Right-tailed Fisher exact test was used to calculate a probability value.
  
  
  RESULTS
  Of 150 proteins that are common for both groups, ingenuity pathways analysis determined 105 proteins that were ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins that are associated with cardiovascular disease. Within this cluster, the most abundant proteins were associated with vascular disease, atherosclerosis, and atherosclerotic lesions. Other top disease clusters were inflammatory response, organismal injury and abnormalities, and hematologic and metabolic disease.
  
  
  CONCLUSIONS
  Exposure to sFlt1-induced preeclampsia alters multiple biologic functions in mothers that persist later in life. Our results suggest that some of the long-term adverse outcomes that are associated with preeclampsia actually may be a consequence rather than a mere unmasking of an underlying predisposition. If similar results are found in humans, the development of preventive strategies for preeclampsia should also improve long-term maternal health.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Egle
authors.initials: E
authors.lastname: Bytautiene
authors.forename: Nataliya
authors.initials: N
authors.lastname: Bulayeva
authors.forename: Geeta
authors.initials: G
authors.lastname: Bhat
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Rosenblatt
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D005260:Female; D013058:Mass Spectrometry; D051379:Mice; D011225:Pre-Eclampsia / Q000097:blood* / Q000209:etiology; D011247:Pregnancy; D020543:Proteome / Q000378:metabolism*; D011897:Random Allocation; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D015415:Biomarkers; D020543:Proteome; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1