In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function.
OBJECTIVE
Emerging data demonstrate that maternal diabetes has long-term health consequences for offspring, including the development of hypertension. In adults, circulating endothelial progenitor cells (EPCs) participate in vascular repair, and EPC numbers and function inversely correlate with the risk of developing vascular disease. Therefore, our objectives were to determine whether hyperglycemia or exposure to a diabetic intrauterine environment alters EPC function.


METHODS
We used well-established clonogenic endothelial colony-forming cell (ECFC) assays and murine transplantation experiments to examine human vasculogenesis.


RESULTS
Both in vitro hyperglycemia and a diabetic intrauterine environment reduced ECFC colony formation, self-renewal capacity, and capillary-like tube formation in matrigel. This cellular phenotype was linked to premature senescence and reduced proliferation. Further, cord blood ECFCs from diabetic pregnancies formed fewer chimeric vessels de novo after transplantation into immunodeficient mice compared with neonatal ECFCs harvested from uncomplicated pregnancies. CONCLUSIONS; Collectively, these data demonstrate that hyperglycemia or exposure to a diabetic intrauterine environment diminishes neonatal ECFC function both in vitro and in vivo, providing potential mechanistic insights into the long-term cardiovascular complications observed in newborns of diabetic pregnancies.
Ingram
David A
DA
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Lien
Izlin Z
IZ
Mead
Laura E
LE
Estes
Myka
M
Prater
Daniel N
DN
Derr-Yellin
Ethel
E
DiMeglio
Linda A
LA
Haneline
Laura S
LS
D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D016640:Diabetes, Gestational; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia; D007231:Infant, Newborn; D011247:Pregnancy; D013234:Stem Cells / Q000187:drug effects*
D005947:Glucose