Circulating Leptin and Angiogenic Factors in Preeclampsia Patients

Nakatsukasa, Harushige; Masuyama, Hisashi; Takamoto, Norio; Hiramatsu, Yuji

doi:10.1507/endocrj.k07e-136

Cited by 40 publications

(30 citation statements)

References 41 publications

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“…53,54 The latter is characterized by lower sFlt-1/PlGF ratio, and adipocytokines, such as adiponectin, might also be involved in its pathogenesis. 55,56 It is notable that the majority of our pre-eclamptic patients were overweight, had late onset (X34 weeks) and mild form of the disease, which might also account for the observed sensitivity and specificity values.…”

Section: Discussionmentioning

confidence: 92%

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

et al. 2010

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The purpose of this study was to determine whether increased serum soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in pre-eclampsia are related to the clinical features and laboratory parameters of the patients, including markers of inflammation, endothelial activation and injury, oxidative stress and trophoblast debris. A total of 54 pre-eclamptic patients, 58 healthy pregnant and 52 healthy non-pregnant women were involved in this case-control study. Serum sFlt-1 and PlGF levels were measured by electrochemiluminescence immunoassay. Serum levels of sFlt-1 and PlGF were significantly higher in pre-eclamptic patients and healthy pregnant women than in healthy non-pregnant women. In addition, pre-eclamptic patients had significantly higher sFlt-1 levels and significantly lower PlGF concentrations compared with healthy pregnant women. According to the subgroup analyses, sFlt-1 levels were significantly higher in severely pre-eclamptic patients than in those with mild pre-eclampsia, whereas pre-eclamptic patients with fetal growth restriction or preterm onset of the disease had significantly lower PlGF concentrations compared with those without intrauterine growth restriction or with a disease onset at term. In the pre-eclamptic group, there were significant positive correlations between serum sFlt-1 levels and systolic and diastolic blood pressure, serum levels of blood urea nitrogen and creatinine, as well as plasma levels of von Willebrand factor antigen, fibronectin and cell-free fetal DNA. Furthermore, serum PlGF concentrations of pre-eclamptic patients showed significant positive correlations with gestational age at disease onset and delivery, as well as with fetal birth weight, and significant inverse correlations with levels of blood urea nitrogen, creatinine and fibronectin. In conclusion, increased serum sFlt-1 and decreased PlGF levels are associated with blood pressure, renal and endothelial dysfunction, trophoblast deportation, as well as with a shorter duration of pregnancy, fetal growth restriction, the severity and preterm onset of the disease in pre-eclampsia. These findings indicate the central role of an angiogenic imbalance in the pathogenesis of this pregnancy-specific disorder.

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Section: Discussionmentioning

confidence: 92%

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

et al. 2010

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“…28 Placental leptin production is elevated under hypoxic conditions, 29 and leptin levels in PE are significantly higher than in normal pregnancies, [30][31][32] suggesting that leptin derived from the placenta may play a role in the pathophysiology of PE through insulin resistance, autonomic activation or direct effects on the endothelium. Next, we investigated whether there were significant differences in adipocytokines in women with early-and late-onset PE and in healthy pregnant women.…”

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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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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“…Recent reports have demonstrated that plasma adiponectin and leptin concentrations are not elevated in normal human pregnancies, but are elevated in women with preeclampsia [19,[25][26][27][28][29]. Specially, adiponectin was increased only in women with late-onset preeclampsia [17,30], and significant differences in adiponectin levels were found between normal and overweight women only among those with late-onset preeclampsia [17].…”

Section: Homa-ir In Patients With Early-and Late-onset Preeclampsia Amentioning

confidence: 98%

Retinol-binding protein 4 and insulin resistance in preeclampsia

2011

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PreeclamPsia is a pregnancy-specific and multisystem disorder characterized by the onset of high blood pressure and proteinuria, which develop after 20 weeks of gestation in previously normotensive women or which are superimposed on preexisting hypertension. In severe cases, several other symptoms, such as renal and/or liver failure and eclampsia, complicate the clinical features. In addition, it can also complicate pregnancies with fetal growth restriction, with nonreassuring fetal status or even those with fetal death. It occurs in about 5% of all pregnancies and results in substantial maternal and neonatal morbidity and mortality [1,2].It is widely accepted that physiological insulin resistance persists in pregnant women, so glucose toler- abstract. Preeclampsia is characterized by the onset of high blood pressure and proteinuria during pregnancy, which results in substantial maternal and neonatal morbidity and mortality. Insulin resistance has been observed before the onset of preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, has been shown to be a potential regulator of insulin resistance originating from adipose tissue. Here we measured insulin resistance and RBP-4 levels in patients with preeclampsia and in women with normal pregnancies matched for gestational age and body mass index at Okayama University Hospital. Our aim was to examine the potential role of RBP4 in the pathophysiology of this disorder. There were no significant differences in RBP4 levels between all patients with preeclampsia and controls. However, the RBP4 level and homeostasis model assessment as an index of insulin resistance (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly higher than in overweight controls carrying normal pregnancies and in normal weight women with late-onset preeclampsia. In contrast, there were no significant differences between the overweight and normal weight groups among patients with early-onset preeclampsia and in healthy pregnant women. These data suggest that RBP4 might act in the pathophysiology of late-onset preeclampsia via increased insulin resistance in obese women.Key words: Preeclampsia, Insulin resistance, Retinol binding protein 4 ance might be lower than in the nonpregnant state. Maternal characteristics such as obesity, diabetes and insulin resistance increase the risk for preeclampsia [3][4][5]. Thus, insulin resistance has been observed before the onset of preeclampsia and has been implicated in its pathophysiology [6][7][8]. Adipocytokines such as tumor necrosis factor-α, leptin and adiponectin have been demonstrated to play a role in the regulation of glucose metabolism and insulin resistance in nonpregnant and pregnant women [9][10][11]. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, was shown to be correlated with insulin resistance [12]. Moreover, it was reported that circulating RBP4 was elevated in a mouse model for insulin resistance...

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Circulating Leptin and Angiogenic Factors in Preeclampsia Patients

Cited by 40 publications

References 41 publications

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

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

Retinol-binding protein 4 and insulin resistance in preeclampsia

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