Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Abstract

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.

Screening for differential methylation status in human placenta in preeclampsia using a CpG island plus promoter microarray

“…Also, recent research has shown that angiogenic factors are involved in blood pressure modulation in pregnancy (14). Furthermore, Kulkarni et al (15) recently reported dysregulation of angiogenic factors (vascular endothelial growth factor and placental growth factor) in PE. In our study, we found that certain genes related to angiogenic and anti-angiogenic functions had aberrant DNA methylation profiles, including HOXD1 (16), DIRAS3 (10) and CXCL1 (17).…”

Interplay between Vascular Endothelial Growth Factor (VEGF) and Nuclear Factor Erythroid 2-related Factor-2 (Nrf2)

“…Several recently published studies have suggested that decreasing VEGF levels might result in placental oxidative stress in preeclampsia (13,35,36). Experimental animal studies have demonstrated that elevated maternal sFlt-1 and decreased VEGF concentrations result in increased oxidative stress (14).…”

“…However, Nrf2 might not be a direct sub- strate of ERK1/2. Instead, it has been suggested that ERK1/2 phosphorylates the nuclear transcription co-activator CBP (cAMP-responsive element-binding protein-binding protein) and that CBP enhances the Nrf2 transcriptional response (35,36). In addition, BeWo cells were stimulated with VEGF, and the phosphorylation status of ERK1/2 was analyzed to substantiate the activation status of the kinases (Fig.…”

Redefining Preeclampsia Using Placenta-Derived Biomarkers

“…[35][36][37]98,119,[132][133][134][135][136][137][138][139][140][141][142][143][144][145][146][147] Figure 1 Maternal plasma was collected at the time of preeclampsia diagnosis (black triangles) or fetal growth restriction (FGR; black squares). The FGR cases were selected, because they also had placental histopathologic abnormalities indicative of poor perfusion.…”