Gui Juan, Potthast Arne, Rohrbach Anne, Borns Katja, Das Anibh M, von Versen-Höynck Frauke
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Pediatr Res. 2016 May;79(5):788-98. doi: 10.1038/pr.2015.269. Epub 2015 Dec 30.
Gestational diabetes (GDM) has long-term consequences for the offspring. Sirtuins (SIRTs) are associated with vascular and metabolic functions. We studied the impact of GDM on SIRT activity and expression in fetal endothelial colony-forming cells (ECFCs) and human umbilical vein endothelial cells (HUVECs) from pregnancies complicated by GDM.
ECFCs and HUVECs were isolated from cord and cord blood of 10 uncomplicated pregnancies (NPs) and 10 GDM pregnancies. Nicotinamidadenindinukleotid (NAD(+)) concentration, SIRT1 and SIRT3 activity, transcription levels of SIRT1, SIRT3, and SIRT4, and protein levels of SIRT1, SIRT3, and SIRT4 were determined in vitro with or without SIRT activators resveratrol (RSV) and paeonol.
Fetal ECFCs from GDM pregnancies showed a decreased NAD(+) concentration, reduced SIRT1 and SIRT3 activity, and lower transcription levels of SIRT1, SIRT3, and SIRT4. HUVECs from GDM pregnancies had decreased NAD(+) concentrations and transcription levels of SIRT1 and SIRT4. RSV markedly enhanced the expression and activity of SIRTs in ECFCs and HUVECs, while paeonol was active only in ECFCs.
A reduction of SIRT activity and expression in fetal endothelial cells provides potential mechanistic insights into the pathophysiology of long-term cardiovascular complications observed in the offspring of GDM pregnancies. SIRT activators can increase SIRT activity in ECFCs, which opens perspectives for new therapeutic targets.
妊娠期糖尿病（GDM）会对后代产生长期影响。沉默调节蛋白（SIRTs）与血管和代谢功能相关。我们研究了GDM对来自GDM合并妊娠的胎儿内皮祖细胞（ECFCs）和人脐静脉内皮细胞（HUVECs）中SIRT活性和表达的影响。
从10例无并发症妊娠（NP）和10例GDM妊娠的脐带和脐血中分离出ECFCs和HUVECs。在有或没有SIRT激活剂白藜芦醇（RSV）和丹皮酚的情况下，体外测定烟酰胺腺嘌呤二核苷酸（NAD(+)）浓度、SIRT1和SIRT3活性、SIRT1、SIRT3和SIRT4的转录水平以及SIRT1、SIRT3和SIRT4的蛋白水平。
GDM妊娠的胎儿ECFCs显示NAD(+)浓度降低、SIRT1和SIRT3活性降低，以及SIRT1、SIRT3和SIRT4的转录水平降低。GDM妊娠的HUVECs的NAD(+)浓度以及SIRT1和SIRT4的转录水平降低。RSV显著增强了ECFCs和HUVECs中SIRTs的表达和活性，而丹皮酚仅在ECFCs中有活性。
胎儿内皮细胞中SIRT活性和表达的降低为GDM妊娠后代中观察到的长期心血管并发症的病理生理学提供了潜在的机制见解。SIRT激活剂可增加ECFCs中的SIRT活性，这为新的治疗靶点开辟了前景。
