Abstract
ObjectiveThe aim of this study was to determine subclinical inflammation in umbilical vein derived endothelial cells (HUVECs) obtained from Asian Indian subjects with gestational diabetes (GDM) and to determine levels of angiogenic factors and arginase activity in their cord blood. MethodsThis case-control study included 38 control and 30 GDM subjects. Subjects were confirmed as GDM based on 75g oral glucose tolerance test (OGTT) conducted in the second trimester of pregnancy. Angiogenic markers and arginase activity were measured in cord blood by ELISA and colorimetric methods respectively. Endothelial inflammation was assessed through adhesion of PKH26-labelled leukocytes onto HUVEC monolayer obtained from the study groups. Gene and surface expression of adhesion molecules were confirmed via reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry respectively. ResultsThe study revealed increased adhesion of leukocytes to HUVECs isolated from GDM subjects compared to controls. HUVECs of babies born to GDM mothers had increased surface and mRNA expression of E-selectin. sTie2 levels were significantly higher in the cord blood for GDM subjects (3869 ± 370 ng/L) compared to controls (3045 ± 296 ng/L). Furthermore, arginase activity was higher in cord blood of GDM mothers as opposed to the control group (7.75 ± 2.4 µmoles of urea/ml/hour vs 2.88 ±0.49 µmoles of urea/ml/hour; p-value= 0.019). Spearman’s correlation analysis revealed positive correlation of cord blood arginase activity with glucose intolerance (ρ=0.596, p=0.004) and post load glucose values (ρ=0.472, p=0.031) of mothers observed during the second trimester of pregnancy.ConclusionsHUVECs derived from Asian Indian GDM mothers, exhibit signs of sub-clinical endothelial inflammation along with increased levels of sTie2 and arginase activity in their cord blood serum.
Highlights
Angiopoietins and vascular endothelial growth factor (VEGF) play major roles in placental growth and embryonic angiogenesis [1,2]
Gestational diabetes imposes a great challenge for gynaecologists due to increased risk of the mother and the child developing overt diabetes and associated vascular complications [10,37,38]
In the current study we observed increased adherence of peripheral blood derived leukocytes to human umbilical vein derived endothelial cells (HUVECs) derived from Asian Indian gestational diabetes mellitus subjects (GDM) cords even in absence of pro-inflammatory cytokines in the culture medium, thereby reflecting enhanced endothelial inflammation in foetal vasculature
Summary
Angiopoietins and vascular endothelial growth factor (VEGF) play major roles in placental growth and embryonic angiogenesis [1,2]. Angiopoietin-1 (Ang-1) via Tie signalling mediates endothelial survival, stabilization and anti-inflammatory functions. Angiopoietin-2 (Ang-2) acts as an Ang-1 antagonist by binding to the Tie receptor and induces vascular leakage, inflammation and cancer metastasis [3]. Circulating levels of Ang-2 is a promising marker of early cardiovascular diseases and endothelial inflammation [5,6]. With increasing gestational age, the Ang-1 levels increase in the amniotic fluid while those of Ang-2 decreases in normal pregnancy. For women with intra-amniotic inflammation, levels of Ang-2 and sTie are increased in the amniotic fluid [7]. Serum levels of angiopoietin related growth factor (AGF) were shown to be elevated during the third trimester in gestational diabetes [8] not much is known about the levels of angiopoietins in cord blood of healthy and gestational diabetes mellitus subjects (GDM)
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