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

Masuyama, Hisashi; Segawa, Tomio; Sumida, Yoshio; Masumoto, Akio; Inoue, Sumito; Akahori, Yasushi; Hiramatsu, Yuji

doi:10.1111/j.1471-0528.2009.02453.x

Cited by 106 publications

(98 citation statements)

References 46 publications

(72 reference statements)

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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]. These data show that there is dysregulation of adipocytokines, including adiponectin and RBP4, among obese women with late-onset preeclampsia.…”

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

confidence: 60%

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

confidence: 60%

Retinol-binding protein 4 and insulin resistance in preeclampsia

2011

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“…18,25,29 Although small sample size is another limitation of our study, management and follow-up were standardized, PE was diagnosed in all of the cases by 1 investigator (P.A. ), and data collection was complete, with almost all of the subjects contributing both clinical and laboratory information at all of the time points.…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Factors in Superimposed Preeclampsia

et al. 2012

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Abstract-Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (Ͻ34 weeks) in 9 and later onset (Ն34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (Pϭ0.001) or who developed late-onset preeclampsia (Pϭ0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Key Words: superimposed preeclampsia Ⅲ angiogenic factors Ⅲ chronic hypertension in pregnancy P reeclampsia (PE), a syndrome that manifests in the latter half of pregnancy and is characterized by maternal hypertension and proteinuria, develops in Ϸ3% to 5% of pregnant women. 1 PE may also develop in women with chronic (preexisting) hypertension and occurs 3 to 5 times more frequently compared with women who are normotensive at conception. [2][3][4] The diagnosis of superimposed PE (SPE) is often difficult, because women already have hypertension and some even have proteinuria. SPE is associated with even greater maternal and fetal morbidity and mortality than PE in women without preexisting hypertension. 2,5 The pathogenesis of PE, as well as SPE, is likely to involve placental vascular remodeling, leading to defective placentation, 6,7 placental ischemia, 8,9 and maternal endothelial cell dysfunction. 10 Emerging data suggest that placental ischemia is associated with increased production of placental proteins, which, on release into the maternal circulation, cause maternal systemic inflammation and endothelial cell dysfunction. 11,12 In particular, an imbalance in circulating proangiogenic and antiangiogenic factors released by the hypoxic placenta has gained currency as a critical link between placental dysfunction and several maternal manifestations of PE, particularly endothelial dysfunction and proteinuria. 13 Results from clinical trials suggest that the soluble forms of the vascular endothelial ...

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“…5,12,36,43 Furthermore, the sFlt-1/PlGF ratio in early-onset preeclampsia has been reported to be higher than that in late-onset preeclampsia. 44 Reports from a recent animal study indicate that the injection of exogenous sFlt-1 in pregnancy induced oxidative stress and hypertension. 25 It is therefore possible that our findings of altered levels of sFlt-1 and its association with fetal outcome may have potential as predictors of preeclampsia.…”

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

Cited by 106 publications

References 46 publications

Retinol-binding protein 4 and insulin resistance in preeclampsia

Retinol-binding protein 4 and insulin resistance in preeclampsia

Angiogenic Factors in Superimposed Preeclampsia

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

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