title: Gestational diabetes induces alterations of sirtuins in fetal endothelial cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Gui
authors.affiliation: Department of Pediatrics, Hannover Medical School, Hannover, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Potthast
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Rohrbach
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Borns
authors.affiliation: Department of Pediatrics, Hannover Medical School, Hannover, Germany.
authors.forename: Anibh M
authors.initials: AM
authors.lastname: Das
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: von Versen-Höynck
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016640:Diabetes, Gestational / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D009243:NAD / Q000737:chemistry; D011247:Pregnancy; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D024101:Mitochondrial Proteins; D009243:NAD; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C525357:SIRT4 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins