Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure?
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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/409432 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832560768219873280 |
|---|---|
| author | Anna C. Roberts Jai Gohil Laura Hudson Kyle Connolly Philip Warburton Rakesh Suman Peter O’Toole David J. O’Regan Neil A. Turner Kirsten Riches Karen E. Porter |
| author_facet | Anna C. Roberts Jai Gohil Laura Hudson Kyle Connolly Philip Warburton Rakesh Suman Peter O’Toole David J. O’Regan Neil A. Turner Kirsten Riches Karen E. Porter |
| author_sort | Anna C. Roberts |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d82e69fbad2e40a69c3165dbc4a8a766 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-d82e69fbad2e40a69c3165dbc4a8a7662025-02-03T01:26:48ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/409432409432Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure?Anna C. Roberts0Jai Gohil1Laura Hudson2Kyle Connolly3Philip Warburton4Rakesh Suman5Peter O’Toole6David J. O’Regan7Neil A. Turner8Kirsten Riches9Karen E. Porter10Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKSchool of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKDepartment of Biology, University of York, York YO10 5DD, UKDepartment of Biology, University of York, York YO10 5DD, UKMultidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKDivision of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UKType 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.http://dx.doi.org/10.1155/2015/409432 |
| spellingShingle | Anna C. Roberts Jai Gohil Laura Hudson Kyle Connolly Philip Warburton Rakesh Suman Peter O’Toole David J. O’Regan Neil A. Turner Kirsten Riches Karen E. Porter Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? Journal of Diabetes Research |
| title | Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? |
| title_full | Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? |
| title_fullStr | Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? |
| title_full_unstemmed | Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? |
| title_short | Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure? |
| title_sort | aberrant phenotype in human endothelial cells of diabetic origin implications for saphenous vein graft failure |
| url | http://dx.doi.org/10.1155/2015/409432 |
| work_keys_str_mv | AT annacroberts aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT jaigohil aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT laurahudson aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT kyleconnolly aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT philipwarburton aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT rakeshsuman aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT peterotoole aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT davidjoregan aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT neilaturner aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT kirstenriches aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure AT kareneporter aberrantphenotypeinhumanendothelialcellsofdiabeticoriginimplicationsforsaphenousveingraftfailure |