Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells.
BACKGROUND
Children born to mothers with gestational diabetes mellitus (GDM) experience increased risk of developing hypertension, type 2 diabetes mellitus, and obesity. Disrupted function of endothelial colony-forming cells (ECFCs) may contribute to this enhanced risk. The goal of this study was to determine whether cord blood ECFCs from GDM pregnancies exhibit altered functionality.


METHODS
ECFCs isolated from the cord blood of control and GDM pregnancies were assessed for proliferation, senescence, and Matrigel network formation. The requirement for p38MAPK in hyperglycemia-induced senescence was determined using inhibition and overexpression studies.


RESULTS
GDM-exposed ECFCs were more proliferative than control ECFCs. However, GDM-exposed ECFCs exhibited decreased network-forming ability in Matrigel. Aging of ECFCs by serial passaging led to increased senescence and reduced proliferation of GDM-exposed ECFCs. ECFCs from GDM pregnancies were resistant to hyperglycemia-induced senescence compared with those from controls. In response to hyperglycemia, control ECFCs activated p38MAPK, which was required for hyperglycemia-induced senescence. In contrast, GDM-exposed ECFCs showed no change in p38MAPK activation under equivalent conditions.


CONCLUSIONS
Intrauterine exposure of ECFCs to GDM induces unique phenotypic alterations. The resistance of GDM-exposed ECFCs to hyperglycemia-induced senescence and decreased p38MAPK activation suggest that these progenitor cells have undergone changes that induce tolerance to a hyperglycemic environment.
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
Emily K
EK
Blue
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
Robert
R
DiGiuseppe
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
Ethel
E
Derr-Yellin
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
Juan Carlos
JC
Acosta
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
S Louise
SL
Pay
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana [3] Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
Helmut
H
Hanenberg
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana.
Megan M
MM
Schellinger
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana.
Sara K
SK
Quinney
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana [3] Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
Julie A
JA
Mund
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana [3] Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
Jamie
J
Case
1] Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana [2] Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana [3] Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana [4] Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana [5] Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
Laura S
LS
Haneline
D000328:Adult; D049109:Cell Proliferation; D016922:Cellular Senescence; D003094:Collagen / Q000737:chemistry; D016640:Diabetes, Gestational / Q000097:blood*; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology*; D004789:Enzyme Activation; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007231:Infant, Newborn; D007797:Laminin / Q000737:chemistry; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011509:Proteoglycans / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases