Abstract
BackgroundAbnormalities of endothelial cell function are proposed to be a critical factor underlying adverse cardiovascular outcomes in the setting of hyperglycaemia. While high-density lipoproteins (HDL) have been demonstrated to be cardioprotective, the impact on the endothelium in hyperglycaemia has not been fully elucidated.MethodsHuman umbilical vein endothelial cells (HUVECs) were exposed to high-glucose conditions using dextrose, the main isoform of glucose, and native HDL. HUVEC proliferation and migration were determined. The key signalling pathways that regulate endothelial cell function were also characterized.ResultsIncreasing concentrations of dextrose resulted in significant reductions in HUVEC proliferation, this was attenuated by coincubation with HDL. In support of this, HDL was also found to rescue dextrose impaired expression of PCNA and the activation (phosphorylation) of the key transcription factor for proliferation ERK. Dextrose also dose-dependently inhibited HUVEC migration, which was mitigated by co-incubation with HDL. Consistent with this, HDL prevented dextrose-induced inhibition of p38 phosphorylation, responsible for cell migration. Finally, phosphorylation of the pro-survival transcription factor Akt was dose-dependently inhibited by dextrose, however, this was completely rescued by co-administration with HDL.ConclusionDextrose-induced hyperglycaemia causes the impairment of endothelial cell proliferation and migration and inhibits the activation of ERK, p38 and Akt pathways. The protective effects of HDL in this milieu highlights the potential for HDL to improve vascular repair in patients with impaired glucose homeostasis.
Highlights
Uncontrolled hyperglycaemia has long been recognized as a major risk factor in the development of vascular complications in diabetic patients [1]
Vascular endothelial cell proliferation and migration are vital in many physiological and pathological processes, such as angiogenesis and healing of the injured endothelium [11]. It has been shown in previous investigations that high glucose exposure in human umbilical vein cells (HUVEC) impairs endothelial function such as insulin signalling [12] and expression of a host of proteins involved in thrombosis and blood viscosity [13]
HUVECs were serum-deprived for 24 h (0.5% foetal bovine serum (FBS)) before the cells were exposed to increasing dextrose concentrations
Summary
Human umbilical vein endothelial cells (HUVECs) were exposed to high-glucose conditions using dex‐ trose, the main isoform of glucose, and native HDL. The key signalling pathways that regulate endothelial cell function were characterized
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