High-density lipoproteins attenuate high glucose-impaired endothelial cell signaling and functions: potential implications for improved vascular repair in diabetes

Cardiovascular Diabetology

Original Investigation

Xing Chen¹  Stephen J. Nicholls²  My-Ngan Duong³  Peter J. Psaltis⁴  Christina A. Bursill⁴ 

[1] Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, 44195, Cleveland, OH, USA;Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, 44195, Cleveland, OH, USA;Heart Health, South Australian Health and Medical Research Institute, 5000, Adelaide, SA, Australia;Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, 44195, Cleveland, OH, USA;Heart Health, South Australian Health and Medical Research Institute, 5000, Adelaide, SA, Australia;South Australian Health and Medical Research Institute, PO Box 11060, 5001, Adelaide, SA, Australia;Heart Health, South Australian Health and Medical Research Institute, 5000, Adelaide, SA, Australia;

关键词: HDL;    Hyperglycaemia;    Endothelial cells;    Atherosclerosis;   

DOI  :  10.1186/s12933-017-0605-8

 received in 2017-07-09, accepted in 2017-09-22,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2017