Giri Hemant, Chandel Shivam, Dwarakanath Linga S, Sreekumar Sooriyakala, Dixit Madhulika
Laboratory of Vascular Biology, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
Sooriya Hospital, Chennai, India.
PLoS One. 2013 Dec 20;8(12):e84546. doi: 10.1371/journal.pone.0084546. eCollection 2013.
The 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.
This 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.
The 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.
HUVECs 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.
本研究旨在确定从患有妊娠期糖尿病（GDM）的亚洲印度裔受试者中获取的脐静脉内皮细胞（HUVECs）中的亚临床炎症，并测定其脐血中血管生成因子水平和精氨酸酶活性。
本病例对照研究纳入了38名对照受试者和30名GDM受试者。根据妊娠中期进行的75g口服葡萄糖耐量试验（OGTT）确诊受试者为GDM。分别采用酶联免疫吸附测定（ELISA）法和比色法测定脐血中的血管生成标志物和精氨酸酶活性。通过PKH26标记的白细胞黏附到从研究组获取的HUVEC单层细胞上，评估内皮炎症。分别通过逆转录聚合酶链反应（RT-PCR）和流式细胞术确认黏附分子的基因表达和表面表达。
研究显示，与对照组相比，从GDM受试者分离出的白细胞对HUVECs的黏附增加。GDM母亲所生婴儿的HUVECs表面E-选择素和mRNA表达增加。与对照组（3045±296 ng/L）相比，GDM受试者脐血中的sTie2水平显著更高（3869±370 ng/L）。此外，与对照组相比，GDM母亲脐血中的精氨酸酶活性更高（7.75±2.4微摩尔尿素/毫升/小时 vs 2.88±0.49微摩尔尿素/毫升/小时；p值 = 0.019）。Spearman相关性分析显示，妊娠中期观察到的母亲脐血精氨酸酶活性与葡萄糖不耐受（ρ = 0.596，p = 0.004）和负荷后血糖值（ρ = 0.472，p = 0.031）呈正相关。
源自亚洲印度裔GDM母亲体内的HUVECs表现出亚临床内皮炎症迹象，同时其脐血血清中的sTie2水平和精氨酸酶活性增加。
