Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice

Egle Bytautiene, Nataliya Bulayeva, Geeta Bhat, Li Li, Kevin P. Rosenblatt, George Saade

Research output: Contribution to journalArticle

30 Citations (Scopus)

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. Study Design: 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. Conclusion: 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume208
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Vascular Endothelial Growth Factor Receptor-1
Proteome
Pre-Eclampsia
Mothers
Metabolic Diseases
Proteins
Cardiovascular Diseases
Immunoglobulin Fc Fragments
Hematologic Diseases
Human Development
Tandem Mass Spectrometry
Vascular Diseases
Adenoviridae
Liquid Chromatography
Mass Spectrometry
Atherosclerosis
Animal Models
Databases
Pregnancy
Wounds and Injuries

Keywords

  • maternal long-term health
  • mice
  • preeclampsia
  • sFlt1

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice. / Bytautiene, Egle; Bulayeva, Nataliya; Bhat, Geeta; Li, Li; Rosenblatt, Kevin P.; Saade, George.

In: American Journal of Obstetrics and Gynecology, Vol. 208, No. 5, 05.2013.

Research output: Contribution to journalArticle

Bytautiene, Egle ; Bulayeva, Nataliya ; Bhat, Geeta ; Li, Li ; Rosenblatt, Kevin P. ; Saade, George. / Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice. In: American Journal of Obstetrics and Gynecology. 2013 ; Vol. 208, No. 5.
@article{88725b7e3c9b4ae0843c35ab985269b5,
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. Study Design: 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. Conclusion: 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.",
keywords = "maternal long-term health, mice, preeclampsia, sFlt1",
author = "Egle Bytautiene and Nataliya Bulayeva and Geeta Bhat and Li Li and Rosenblatt, {Kevin P.} and George Saade",
year = "2013",
month = "5",
doi = "10.1016/j.ajog.2013.01.042",
language = "English (US)",
volume = "208",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "5",

}

TY - JOUR

T1 - Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice

AU - Bytautiene, Egle

AU - Bulayeva, Nataliya

AU - Bhat, Geeta

AU - Li, Li

AU - Rosenblatt, Kevin P.

AU - Saade, George

PY - 2013/5

Y1 - 2013/5

N2 - 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. Study Design: 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. Conclusion: 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.

AB - 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. Study Design: 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. Conclusion: 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.

KW - maternal long-term health

KW - mice

KW - preeclampsia

KW - sFlt1

UR - http://www.scopus.com/inward/record.url?scp=84876667554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876667554&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2013.01.042

DO - 10.1016/j.ajog.2013.01.042

M3 - Article

VL - 208

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 5

ER -