Second-Trimester Maternal Serum Placental Growth Factor and Vascular Endothelial Growth Factor for Predicting Severe, Early-Onset Preeclampsia

Polliotti, Bruno; Fry, Andrea; Saller, Devereux N.; Mooney, Robert A.; Cox, Christopher; Miller, Richard K.

doi:10.1097/00006250-200306000-00022

Cited by 35 publications

(38 citation statements)

References 19 publications

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“…The concentration of serum PlGF in women with PE was decreased significantly, whereas sFlt-1 and sEng levels and the sFlt-1/PlGF ratios in women with PE were increased significantly, compared with those in healthy pregnant women, as reported previously. [16][17][18][19][20][21][22][23] We also observed that the sFlt-1 levels and sFlt-1/PlGF ratios in women with early-onset PE were increased significantly compared with those in women with late-onset PE. The increase in the sFlt-1/PlGF ratios reported here is consistent with a previous report, 24 and we also observed that sEng levels in women with early-onset PE were increased significantly compared with those in women with late-onset PE.…”

Section: Discussionsupporting

confidence: 60%

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Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Masuyama

Segawa

Sumida

et al. 2010

BJOG

109

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Objective Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight.Design A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan.Setting Tertiary referral centre serving 2000 births.Methods Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index.Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/ PlGF ratio, sEng, adiponectin and leptin.Results The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 ± 30.2 versus 45.4 ± 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 ± 18.3 ng/ml versus 26.0 ± 6.7 ng/ml, P = 0.001; late: 39.5 ± 9.2 ng/ml versus 22.0 ± 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 ± 13.4 lg/ml versus 12.0 ± 4.3 lg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia.Conclusions These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early-and late-onset pre-eclampsia.

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Section: Discussionsupporting

confidence: 60%

“…[16][17][18] Moreover, recent reports have indicated that the soluble form of the VEGF receptor-1 (sFlt-1) is increased in the placenta and serum of women with PE. [18][19][20][21] Thus, sFlt-1 may act by sequestering free PlGF and free VEGF, thereby preventing interaction between endothelial Median (interquartile range).…”

Section: Discussionmentioning

confidence: 99%

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Masuyama

Segawa

Sumida

et al. 2010

BJOG

109

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“…2 Indeed, low levels of serum PlGF and VEGF (proangiogenic) and increased levels of sFlt-1 (antiangiogenic) appear to antedate the onset of clinical symptoms. [3][4][5][6][7] In addition to alterations in angiogenesis, however, women who develop preeclampsia also have evidence of insulin resistance. 8,9 Large studies suggest women with pregestational diabetes mellitus 10 and women who develop gestational diabetes mellitus 11 have an increased risk for developing preeclampsia.…”

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confidence: 99%

Insulin Resistance and Alterations in Angiogenesis

et al. 2004

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Abstract-Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule Key Words: pregnancy Ⅲ insulin resistance Ⅲ preeclampsia Ⅲ clinical trials P reeclampsia is associated with considerable maternal and neonatal morbidity and mortality, and although most agree that preeclampsia is an endothelial cell disorder, the pathogenesis of preeclampsia is not well understood. 1 Recently, preeclampsia has been associated with alterations in expression of angiogenesis-related proteins such that administration of placental soluble fms-like tyrosine kinase 1 (sFlt-1), an endogenous inhibitor to vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), to rats resulted in hypertension, proteinuria, and glomerular endotheliosis, a phenotype with similarities to human preeclampsia. 2 Indeed, low levels of serum PlGF and VEGF (proangiogenic) and increased levels of sFlt-1 (antiangiogenic) appear to antedate the onset of clinical symptoms. [3][4][5][6][7] In addition to alterations in angiogenesis, however, women who develop preeclampsia also have evidence of insulin resistance. 8,9 Large studies suggest women with pregestational diabetes mellitus 10 and women who develop gestational diabetes mellitus 11 have an increased risk for developing preeclampsia. Importantly, recent data from in vitro models outside of pregnancy suggest insulin signaling and angiogenesis are intimately related at a molecular level. 12-14 Because both normal insulin signaling and angiogenesis maintain endothelial cell health, it is plausible that women with pre-existing alterations in insulin metabolism have an exaggerated response to alterations in angiogenic factors, and alterations in both pathways may interact to magnify the risk for preeclampsia. In an effort to identify early pregnancy markers that are biologically linked to the pathogenesis of preeclampsia, we tested the hypothesis that an epidemiological interaction exists between insulin resistance and angiogenesis by measuring markers for both in a prospective nested case-control study.

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“…2,5,6 Several studies have shown that these possess superior discriminatory ability than that shown by the authors. 5,7,8 In a comparative study of pre-eclamptic and normotensive pregnancies, we found the circulating sFlt-1 to be significantly increased in PE compared with normotensive pregnancies, 9 whereas the mean PlGF levels were reduced. Receiver operating characteristic curve analysis showed that sFlt-1 and sFlt-1:PlGF ratio cutoffs of 15.7 and 92.2 ng ml À1 , respectively, were able to distinguish PE from normotensive pregnancies with 100% sensitivity and specificity.…”

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confidence: 78%

Angiogenic balance and diagnosis of pre-eclampsia: selecting the right VEGF receptor

et al. 2011

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We read with interest the report by Rath and Tripathi 1 in which they have evaluated the levels of serum vascular endothelial growth factor (VEGF) and soluble VEFR receptor type 2 in hypertensive disorders of pregnancy. Their findings are certainly intriguing. First, they found increased VEGF levels in pre-eclampsia (PE) and eclampsia. This is contrary to what has been noted in almost all published reports that show reduced VEGF levels. [2][3][4][5] In our investigations, we have consistently found circulating VEGF levels to be undetectable in PE/eclampsia. The basis for this reduction is also well defined. There is ample evidence to prove that circulating VEGF as well as placental growth factor (PlGF) are bound to the excess soluble fms-like tyrosine kinase-1 (sFlt-1) or sVEGFR-1 that is produced by the preeclamptic placenta. 2 There is a close relationship between the elevated sFlt-1 and the reduction in VEGF and PlGF. The authors have not discussed this major difference between published reports and their findings. It is unclear whether the kit used in their study measured free or total (free as well as that bound to sFLt-1) VEGF. If it measures both forms of VEGF, then the total levels could be elevated. 3 This distinction is critical, however, as it is only the free VEGF that is biologically available. Interestingly, their explanation of the reduced sVEGRF2 level is based on the premise that this reflects receptor downregulation as a result of excess VEGF.Also of interest is their decision to evaluate sVEGFR2 as a diagnostic marker. The hypothesis behind the utility of this molecule as a diagnostic marker is unclear. In contrast the biological basis behind alterations in sFlt-1 in PE has been well studied. A large number of studies, both experimental and human, have shown consistent increases in sFlt-1 in PE, and have suggested using it either alone or in combination with serum PlGF (as sFlt-1:PlGF ratio) to differentiate PE from other hypertensive disorders of pregnancy. 2,5,6 Several studies have shown that these possess superior discriminatory ability than that shown by the authors. 5,7,8 In a comparative study of pre-eclamptic and normotensive pregnancies, we found the circulating sFlt-1 to be significantly increased in PE compared with normotensive pregnancies, 9 whereas the mean PlGF levels were reduced. Receiver operating characteristic curve analysis showed that sFlt-1 and sFlt-1:PlGF ratio cutoffs of 15.7 and 92.2 ng ml À1 , respectively, were able to distinguish PE from normotensive pregnancies with 100% sensitivity and specificity. PlGF alone had a slightly lower performance (cutoff 177.1 pg ml À1 ; AUC ¼ 98.3%; 95% CI 96.9-99.7).Apart from the fact that the findings are difficult to understand, some conclusions made in the paper seem to be overinterpretation of findings. These include suggestions of a 'role' for sVEGFR2 in the pathogenesis of PE, and that sVEGFR2 reflects endothelial health or endothelial progenitor cell regenerative ability. It is difficult to find the biological significance o...

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Second-Trimester Maternal Serum Placental Growth Factor and Vascular Endothelial Growth Factor for Predicting Severe, Early-Onset Preeclampsia

Cited by 35 publications

References 19 publications

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Insulin Resistance and Alterations in Angiogenesis

Angiogenic balance and diagnosis of pre-eclampsia: selecting the right VEGF receptor

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