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    Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure?

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    Publication date
    2015
    Author
    Roberts, A.C.
    Gohil, J.
    Hudson, L.
    Connolly, K.
    Warburton, P.
    Suman, R.
    O'Toole, P.
    O'Regan, D.J.
    Turner, N.A.
    Riches-Suman, Kirsten
    Porter, K.E.
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    Keyword
    Type 2 diabetes (T2DM); Endothelial dysfunction; Coronary heart disease; Saphenous vein graft failure
    Rights
    © 2015 The Authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Peer-Reviewed
    yes
    
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    Abstract
    Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.
    URI
    http://hdl.handle.net/10454/10083
    Version
    published version paper
    Citation
    Roberts AC, Gohil J, Hudson L et al (2015) Aberrant phenotype in human endothelial cells of diabetic origin: Implications for saphenous vein graft failure? Journal of Diabetes Research. Article ID 409432: 12 pages.
    Link to publisher’s version
    http://dx.doi.org/10.1155/2015/409432
    Type
    Article
    Collections
    Life Sciences Publications

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