Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft\nfailure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from\nT2DMand nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) ECwere\ncompared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed;\nwestern blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia,\nTNF-????, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration\n(?30%) and angiogenesis (?40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant\ninhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC\nfunction, but TNF-???? and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt\ninhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study\nhighlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and longterm\ndysfunction to the homeostatic capacity of the endothelium.
Loading....