pose danger to the ongoing vasculogenic processes in the developing foetus of GDM subjects. Hence, one can envisage that uncontrolled glycemic status along with inflammatory mediators in placental circulation during GDM will lead to an unopposed release of sTie2, which in turn, may contribute to a leaky GSK126 feto-placental vasculature thereby enhancing passage of inflammatory mediators from maternal to foetal circulation. This 6 Sub-Clinical Inflammation in Gestational Diabetes Parameters Angiopoietin 1 Angiopoietin 2 Arginase Activity Tie 2 VEGF P < 0.05 versus controls. Control GDM P- value 6495 179 1972 262 2.88 0.49 3045 296 329 61 6796 132 1925 333 7.75 2.4 0.2145 0.9111 0.0151 3869 370 0.0464 287 49 0.6178 doi: 10.1371/journal.pone.0084546.t002 Parameters Glucose Intolerance Fasting Glucose Post load Glucose Cord Blood Parameters Angiopoietin 1 Angiopoietin 2 Tie 2 VEGF Correlation coefficient 0.596 0.349 0.472 0.296 0.244 0.308 0.100 p value 0.004 0.121 0.031 0.192 0.287 0.175 0.666 Serum glucose values 7.8mmol/l at 2 hours of 75g OGTT were considered as impaired glucose tolerance according to Diabetes in Pregnancy Study group India guidelines. For Correlation analysis, presence and absence of glucose intolerance was assigned the binary numerical system of 1 and 0 respectively. doi: 10.1371/journal.pone.0084546.t003 may further trigger endothelial dysfunction in foetal 26148857 blood vessels to cause future cardiovascular complications. However, more detailed cross-sectional and longitudinal studies are required to confirm this speculation. Increased arginase activity in the peripheral blood is reported for type 2 diabetic and breast cancer patients, and its inhibition gives protection from myocardial infarction in rats. In normal pregnancy, results are contradictory, with both 
increased and decreased activity being reported. For the current study we observed a significant increase for arginase activity in the cord blood serum of babies born to GDM women. Increased arginase activity in cord blood serum would limit arginine bioavailability and may consequently cause NO deficiency in vascular cells. This could also explain increased eNOS expression in HUVECs obtained from GDM women as a compensatory response to increased arginase activity. Since L-arginine is required to inhibit platelet aggregation and for pregnancy associated immune-tolerance, depletions in its levels, will also have serious consequences on foetal health. This is exemplified by that fact that enhanced arginase activity contributes to intimal hyperplasia and coronary vascular dysfunction in type2 diabetic animals. Initiation of cardiovascular dysfunction occurs in third trimester itself, as reported in a recent study where foetal heart ventricular contractility was reduced for GDM subjects compared to normal pregnancies. These findings suggest that the aberrant foeto-placental environment along with a pro-inflammatory endothelium during second trimester may significantly influence the vascular function of the developing foetus. Among the two known isoforms of arginases, the cytosolic arginase is anti-inflammatory while the mitochondrial isoform arginase II, promotes inflammation through mitochondrial reactive oxygen species. Despite our repeated efforts we failed to detect any measurable differences in the mRNA levels of arginase II in HUVECs derived from GDM 2435173 women, indicating that the likely source for increased arginase activity are the circulating monocytes and macrophages.
