Maternal serum soluble fms-like tyrosine kinase 1 concentrations are not increased in early pregnancy and decrease more slowly postpartum in women who develop preeclampsia

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
American Journal of Obstetrics and Gynecology (Impact Factor: 3.97). 08/2005; 193(1):185-91. DOI: 10.1016/j.ajog.2004.11.038
Source: PubMed

ABSTRACT We measured maternal serum soluble fms-like tyrosine kinase 1 concentrations across pregnancy and immediately postpartum in women who developed preeclampsia and normal pregnant women.
This was a nested case control study of 113 normal pregnant women and 55 women with preeclampsia.
Serum soluble fms-like tyrosine kinase 1 concentrations increased similarly in early pregnancy in both groups. Mean serum soluble fms-like tyrosine kinase 1 concentrations were increased in women who developed preeclampsia, compared with normal pregnant women, and this increase was most pronounced in severe preeclampsia. However, many women with preeclampsia had soluble fms-like tyrosine kinase 1 concentrations similar to normal pregnant women. Lastly, soluble fms-like tyrosine kinase 1 decreased rapidly after delivery, but this decrease was significantly slower in women with severe preeclampsia.
Increased soluble fms-like tyrosine kinase 1 is not an early-pregnancy event among women who later develop preeclampsia. Increased soluble fms-like tyrosine kinase 1 is more likely to be present in women with severe preeclampsia, but it is not present in all women with preeclampsia. Soluble fms-like tyrosine kinase 1 concentrations decrease more slowly after delivery in women with preeclampsia, consistent with a decreased rate of excretion or continued production.

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is strong evidence that overproduction of soluble fms-like tyrosine kinase-1 (sFLT1) in the placenta is a major cause of vascular dysfunction in preeclampsia through sFLT1-dependent antagonism of VEGF. However, the cause of placental sFLT1 upregulation is not known. Here we demonstrated that in women with preeclampsia, sFLT1 is upregulated in placental trophoblasts, while VEGF is upregulated in adjacent maternal decidual cells. In response to VEGF, expression of sFlt1 mRNA, but not full-length Flt1 mRNA, increased in cultured murine trophoblast stem cells. We developed a method for transgene expression specifically in mouse endometrium and found that endometrial-specific VEGF overexpression induced placental sFLT1 production and elevated sFLT1 levels in maternal serum. This led to pregnancy losses, placental vascular defects, and preeclampsia-like symptoms, including hypertension, proteinuria, and glomerular endotheliosis in the mother. Knockdown of placental sFlt1 with a trophoblast-specific transgene caused placental vascular changes that were consistent with excess VEGF activity. Moreover, sFlt1 knockdown in VEGF-overexpressing animals enhanced symptoms produced by VEGF overexpression alone. These findings indicate that sFLT1 plays an essential role in maintaining vascular integrity in the placenta by sequestering excess maternal VEGF and suggest that a local increase in VEGF can trigger placental overexpression of sFLT1, potentially contributing to the development of preeclampsia and other pregnancy complications.
    Journal of Clinical Investigation 10/2014; 124(11). DOI:10.1172/JCI76864 · 13.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate the association between cigarette use during pregnancy and pregnancy-induced hypertension/preeclampsia/eclampsia (PIH) by maternal race/ethnicity and age. Methods This retrospective cohort study was based on the U.S. 2010 natality data. Our study sample included U.S. women who delivered singleton pregnancies between 20 and 44 weeks of gestation without major fetal anomalies in 2010 (n = 3,113,164). Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios and the corresponding 95% confidence intervals. Results We observed that the association between maternal smoking and PIH varied by maternal race/ethnicity and age. Compared with non-smokers, reduced odds of PIH among pregnant smokers was only evident for non-Hispanic white and non-Hispanic American Indian women aged less than 35 years. Non-Hispanic Asian/Pacific Islander women who smoked during pregnancy had increased odds of PIH regardless of maternal age. Non-Hispanic white and non-Hispanic black women 35 years or older who smoked during pregnancy also had increased odds of PIH. Conclusion Our study findings suggest important differences by maternal race/ethnicity and age in the association between cigarette use during pregnancy and PIH. More research is needed to establish the biologic and social mechanisms that might explain the variations with maternal age and race/ethnicity that were observed in our study.
    PLoS ONE 10/2014; 9(10):e106446. DOI:10.1371/journal.pone.0106446 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypertensive disorders of pregnancy (HDP) constitute the most common medical condition seen during gestation, effecting 1 in 10 pregnancies in the USA. Traditionally, preeclampsia (PE) is defined as a new onset of hypertension and either proteinuria or end-organ dysfunction after 20 weeks of gestation in a previously normotensive woman. Preeclampsia is a potentially life-threatening condition with widespread underlying endothelial dysfunction, and accompanying inflammation, vasoconstriction, and platelet activation. Women with preeclampsia are at an increased risk for life-threatening complications and progression to eclampsia. Worldwide, 10 to 15 % of maternal deaths are from preeclampsia and related complications. Traditionally, diagnosis of preeclampsia is made based upon presence of risk factors and clinical criteria. Diagnosis is challenging in asymptomatic women early in pregnancy as well as in nulliparous women as they lack obstetric history; however, it is well known that women with previous preeclampsia have a 14.7 % risk of the condition in the second pregnancy. Prediction of those at risk and early diagnosis is crucial to enable close surveillance of high-risk women in order to improve maternal and fetal outcomes. There has been much advance in our understanding of the pathogenesis of PE and in the field of angiogenic markers. However, no one test meets the criteria for a good biomarker. A multiparametric approach appears to be optimal as we await newer systems biology approaches to give us better insight into the pathogenesis of the disease.
    Current Hypertension Reports 11/2014; 16(11):491. DOI:10.1007/s11906-014-0491-3 · 3.90 Impact Factor