MacKenzie, R.M. et al. (2013) Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes. Clinical Science, 124(6), pp. 403-411. (doi: 10.1042/CS20120239)
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Abstract
The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H2O2 and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ10 significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dymott, Dr Jane and Hamilton, Dr Carlene and Dominiczak, Professor Anna and Salt, Dr Ian and Delles, Professor Christian and MacKenzie, Dr Ruth and Miller, Dr William |
| Authors: | MacKenzie, R.M., Salt, I.P., Miller, W.H., Logan, A., Ibrahim, H.A., Degasperi, A., Dymott, J.A., Hamilton, C.A., Murphy, M.P., Delles, C., and Dominiczak, A.F. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Science and Engineering > School of Computing Science College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Clinical Science |
| Publisher: | Portland Press Ltd. |
| ISSN: | 0143-5221 |
| ISSN (Online): | 1470-8736 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in Clinical Science 124(6):403-411 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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