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

• Published in: Cardiovascular diabetology Vol. 16; no. 1; p. 121
• Main Authors: Chen, Xing, Duong, My-Ngan, Psaltis, Peter J, Bursill, Christina A, Nicholls, Stephen J
• Format: Journal Article
• Language: English
• Published: England BioMed Central 29.09.2017; BMC
• Subjects: Activation; AKT protein; Angiogenesis; Apoptosis; Atherosclerosis; Breast cancer; Cell adhesion & migration; Cell growth; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cells, Cultured; Cholesterol; Dextrose; Diabetes; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus - metabolism; Disease; Dose-Response Relationship, Drug; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium; Glucose; Glucose - toxicity; HDL; High density lipoprotein; Homeostasis; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hyperglycaemia; Hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; Kinases; Lipoproteins; Lipoproteins, HDL - pharmacology; Lipoproteins, HDL - therapeutic use; Metabolism; Migration; Original Investigation; Phosphorylation; Proliferating cell nuclear antigen; Proteins; Pulmonary arteries; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Umbilical vein; United States > US; HDL; Hyperglycaemia; Endothelial cells; Atherosclerosis
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-017-0605-8

Abnormalities 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. Human 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. Increasing 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. Dextrose-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.