Glucose attenuates hypoxia-induced changes in endothelial cell growth by inhibiting HIF-1α expression.
Hyperglycaemia and hypoxia play essential pathophysiological roles in diabetes. We determined whether hyperglycaemia influences endothelial cell growth under hypoxic conditions in vitro. Using a Ruskinn Invivo2400 Hypoxia Workstation, bovine aortic endothelial cells (BAEC) were exposed to high glucose concentrations (25 mM glucose) under normoxic or hypoxic conditions before cell growth (balance of proliferation and apoptosis) was assessed by fluorescence-activated cell sorting (FACS) analysis, proliferating cell nuclear antigen (pCNA), Bcl-xLand caspase-3 protein expression and activity. Hypoxia increased hypoxia response element (HRE) transactivation and induced hypoxia-inducible factor-1α (HIF-1α) expression when compared to normoxic controls concomitant with a significant decrease in cell growth. High glucose (25 mM) concentrations attenuated HRE transactivation and HIF-1α protein expression while concurrently reducing hypoxia-induced changes in BAEC growth. Knockdown of HIF-1α expression significantly decreased hypoxia-induced changes in growth and attenuated the modulatory effects of glucose. These results provide evidence that hypoxia-induced control of BAEC growth can be altered by the presence of glucose via inhibition of HIF-1α expression and activation.
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland.
Wei
W
Gao
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland.
Gail
G
Ferguson
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland Mater Misericordiae Hospital, Institute of Ophthalmology, The Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.
Paul
P
Connell
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland.
Tony
T
Walshe
Mater Misericordiae Hospital, Institute of Ophthalmology, The Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.
Colm
C
O'Brien
Department of Surgery, University of Rochester, Rochester, NY, USA.
Eileen M
EM
Redmond
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland paul.cahill@dcu.ie.
Paul A
PA
Cahill
Endothelial; HIF-1α; apoptosis; diabetes; hyperglycaemia; hypoxia