Altered Expression of Angiogenic Biomarkers in Pregnancy Associated with Gestational Diabetes

Abstract

Background: Gestational diabetes mellitus (GDM) typically occurs during the third trimester of pregnancy. Maternal hyperglycemic may influence the expression of pro-and antiangiogenic factors. Altered levels of angiogenic biomarkers in GDM pregnant women are associated with abnormal placentation. This study aimed to investigate the rates of expression of five angiogenic biomarkers called vascular endothelial growth factor-A (VEGF-A), angiopoietin-2, endoglin, endothelin-1, and granulocyte colony-stimulating factor (G-CSF) in GDM. Methods: The samples were obtained from normal (n=9) and GDM (n=10) pregnancies. Multiplex assay was used to assess the levels of angiogenic biomarkers including VEGF-A, endoglin, endothelin-1, angiopoietin-2, and G-CSF in serum samples. All data were statistically analyzed using an unpaired Student's t-test. Correlations between measured parameters were made using Pearson correlations. Results: VEGF-A, endoglin, endothelin-1, and angiopoietin-2 levels in GDM were significantly higher (P value = 0.001, 0.042, 0.049, 0.001; respectively) compared to control. However, G-CSF level exhibited a non-significant increase (P=0.466) in GDM compared to healthy controls. There was a significant positive correlation between angiopoietin-2 with endoglin, endothelin-1, and VEGF-A. Moreover, there was a significant positive correlation between VEGF-A with endoglin and endothelin-1. Most interestingly, there was a significant positive correlation between G-CSF with endothelin-1. Conclusion:The angiogenic biomarkers were highly altered in pregnant women with GDM.The study provides a novel advance in the field of gestational diabetes, in terms of increase of angiogenic factors that can modify the vascularization of the placenta, the development of fetal vascular system and the insulin resistance itself.

Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia

“…Multiple blood vessels of the mother pass through the paracrine, while autocrine regulatory substances and environmental effects affect the activity of the placenta [ 27 ], which then affects fetus. Vascular function is clearly abnormal in the context of inflammation and oxidative stress caused by a blood lipid hormone disorder [ 28 , 29 ] and various vascular factors affect the normal growth of blood vessels.…”

“…Data from recent years imply that VEGF is strongly associated with GDM. In some GDM patients with VEGF-A, endothelin and endothelin-1 levels were significantly increased [ 27 ]. VEGF-A, endothelin, and G-CSF (granulocyte colony-stimulating factor) have been shown to have a significant positive correlation with endothelin-1.…”

“…VEGF is not a single factor. Endothelin-1 and colony-stimulating factor in other GDM patients jointly affect vascular health [ 27 ] / VEGFR-1 (Flt-1), VEGFR-2 (KD2) Chile 2017 Lower placental expression levels of Flt-1 (mRNA and protein) are associated with decreased expression of KDR mRNA and increased levels of KDR protein in GDM placenta. In conclusion, GDM is associated with reduced expression of flt-1 Among a variety of receptors, the characteristic expression of GDM is that the low expression of Flt and the high expression of KDR are more significant, and there is a certain influence relationship between the two receptors [ 37 ] VEGF VEGFR-1 (Flt-1), VEGFR-2 (KD2) Brazil 2010 Strong staining of VEGF and VEGFR-2 in vascular and trophoblast cells was limited to trophoblast VEGFR-1; strong staining of VEGFR-1 was observed in vascular cells and trophoblast cells, while VEGF and VEGFR-2 were detected only in trophoblast The expression of different VEGF and its receptor is different in different parts of GDM patients, which can indirectly infer the pathogenesis of VEGF and its receptor and the pathogenesis of the lesion site [ 38 ] VEGF VEGFR-1 (Flt-1), VEGFR-2 (KD2) Japan 2019 GDM or previous GDM, VEGF-R1 was higher than normal and VEGF-R2 was lower than normal.…”

Lower ATG7 Levels are Associated with a Higher Risk of Gestational Diabetes Mellitus: A Cross-Sectional Study

“…In addition, previous studies found that insulin resistance is a major contributor to the development of GDM. 30–32 These findings suggest that ATG7 may mediate insulin resistance in the pathogenesis of GDM.…”

Research progress of placental vascular pathophysiological changes in pregnancy-induced hypertension and gestational diabetes mellitus

“…Only two studies reported that there is no significant difference in ET-1-mediated placental perfusion and vasoconstriction between normal pregnancy and PIH placenta (Inayatulla et al, 1993;Read et al, 1999). Serum ET-1 level in GDM was significantly higher compared to controls (Al-Ofi et al, 2021), while both Swiderski and Beata Telejko, et al showed that plasma ET-1 levels in women with GDM were not significantly different from those observed in pregnant women without GDM (Telejko et al, 2009;Swiderski et al, 2010). Although no relevant studies have been found to prove abnormal plasma ET-1 levels in pregnant women with GDM, some studies have shown that women with GDM are less sensitive to ET-1 than pregnant women without GDM (Ang et al, 2001).…”