Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop

McKeeman, G; Ardill, Joy; Caldwell, Carolyn; Hunter, Alyson; McClure, Neil

doi:10.1016/j.ajog.2004.03.004

Cited by 202 publications

(127 citation statements)

References 24 publications

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“…Several studies carried out in Western countries have consistently reported increased levels of plasma sFlt-1 8,15,[34][35][36][37][38][39][40][41] in mothers with preeclampsia compared with normotensive women. Our results suggest that Indian women with preeclampsia also have a similar increase in plasma sFlt-1 levels.…”

Section: Discussionmentioning

confidence: 99%

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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This study was designed to test the hypothesis that altered angiogenic factors together with increased oxidative stress and reduced docosahexaenoic acid (DHA) levels may be associated with altered birth outcome parameters. To test this hypothesis, levels of plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), the oxidative stress marker malondialdehyde (MDA) and fatty acids were estimated in women with preeclampsia and their cord samples and compared with those in normotensive women. The association of these parameters with birth outcome was also examined. Our results show that in preeclamptic women, maternal plasma VEGF and PlGF levels were lower, whereas sFlt-1 levels were higher (Po0.05 for all) than in normotensive women. In contrast, cord plasma VEGF levels were higher (Po0.05) in preeclamptic women, whereas there was no difference in sFlt-1 levels. Plasma DHA levels in both the mother and cord were lower (Po0.05) in the preeclamptic group compared with normotensive women. Maternal plasma sFlt-1 levels were positively (n¼23, r¼0.415, P¼0.039) associated with MDA concentrations in preeclamptic women. Maternal plasma sFlt-1 levels showed a strong negative association with baby weight (n¼37, r¼À0.547, P¼0.001), head circumference (n¼37, r¼À0.472, P¼0.005) and baby chest circumference (n¼37, r¼À0.375, P¼0.032) in the preeclamptic group. Cord plasma sFlt-1 concentrations were negatively associated with cord plasma DHA concentrations (n¼28, r¼À0.552, P¼0.004). This study suggests that dysregulation of angiogenic factors may be associated with maternal oxidative stress. Increased oxidative stress may reduce cord DHA levels and increase sFlt-1 levels, leading to poor birth outcomes in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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“…This state appears to result from an imbalance in the production and circulating concentrations of angiogenic factors such as placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) and anti-angiogenic factors such as soluble VEGF receptor-1 (sVEGFR-1) and soluble endoglin (sEng). Elevated serum and plasma concentrations of sVEGFR-1 and s-Eng have been observed after the diagnosis of PE [1][2][3][7][8][9]11,12,15,18,19,[21][22][23] and before the recognition of clinical disease [4][5][6]10,13,14,16,17,20,30,32].…”

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confidence: 99%

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Erez

Romero

Espinoza

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, The Journal of Maternal-Fetal & Neonatal Medicine, 21:5, 279-287, DOI: 10.1080 AbstractIntroduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n ¼ 201); (2) patients who delivered an SGA neonate (n ¼ 145); and (3) patients who developed PE (n ¼ 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results.(1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively).(2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4....

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“…20 Literature supports a role for abnormal angiogenesis in the development of preeclampsia. [21][22][23] In a prospective cohort, Levine and colleagues found that sFlt1 levels in women who develop preeclampsia rise above those in women who remain normotensive several weeks before the onset of the clinical syndrome. 24 .…”

Section: Commentmentioning

confidence: 99%

“…High levels of circulating sFlt1 in early pregnancy are associated with development of preeclampsia weeks later. [21][22][23] The sFlt1 is the soluble form of the vascular endothelial growth factor (VEGF) receptor 1 which binds VEGF and other angiogenic factors in the circulation, thereby decreasing their action at the target organs. As further evidence for the role of dysregulation of angiogenesis in the causation of preeclampsia, animal models have been reported where a preeclampsia-like condition is induced with overexpression of sFlt1.…”

Section: Commentmentioning

confidence: 99%

Long-term Alterations in Maternal Plasma Proteome After sFlt1-induced Preeclampsia in Mice

Bytautiene

Bulayeva

Bhat

et al. 2014

Obstetric Anesthesia Digest

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Objective-Preeclampsia (PE) is associated with long-term adverse maternal health, such as cardiovascular (CVD) and metabolic diseases. The objective of this study was to determine whether PE in a well characterized animal model induced by over-expression of sFlt-1 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 carrying sFlt1 or the murine IgG2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography -mass spectrometry assay. The tandem MS data were searched against a mouse database and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool (MaxQuant/Mascot). Results were analyzed using Ingenuity Pathways Analysis (IPA). Right-tailed Fisher's exact test was used to calculate a P-value.Results-Out of 150 proteins common for both groups, IPA determined 105 proteins ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins associated with CVD. 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, hematological and metabolic disease.Conclusions-Exposure to sFlt1-induced preeclampsia alters multiple biological functions in mothers that persist later in life. Our results suggest that some of the long term adverse outcomes associated with preeclampsia may actually be a consequence of an underlying predisposition. If similar results are found in humans, developing preventive strategies for preeclampsia should also improve long term maternal health.

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Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop

Cited by 202 publications

References 24 publications

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Long-term Alterations in Maternal Plasma Proteome After sFlt1-induced Preeclampsia in Mice

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