Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes

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)

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 > Institute of Cardiovascular and Medical Sciences
College of Science and Engineering > School of Computing Science
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
464051Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.Anna DominiczakBritish Heart Foundation (BHF)RG/07/005/23633RI CARDIOVASCULAR & MEDICAL SCIENCES
302342Cardiovascular Functional genomics - Translating experimental work to human diseaseAnna DominiczakWellcome Trust (WELLCOME)066780 EdinburgRI CARDIOVASCULAR & MEDICAL SCIENCES